Transcriptional regulator

ABSTRACT

Genes each encoding a novel transcriptional regulator having a bromodomain have been successfully isolated from a human testis cDNA library using primers prepared based on an EST sequence found using the bromodomain sequence of the transcriptional regulator. These genes are structurally analogous to each other.

[0001] This is a continuation-in-part of PCT/JP98/01783, filed Apr. 17, 1999, and claims priority from Japanese Application Nos. 9/116570, filed Apr. 18, 1997, and 9/310027, filed Oct. 24, 1997.

TECHNICAL FIELD

[0002] The present invention relates to a novel transcriptional regulator containing a bromodomain and a gene encoding it.

BACKGROUND ART

[0003] The bromodomain is a characteristic motif of proteins found in transcriptional regulators. Proteins having a bromodomain usually contain one or two (Tamkun, J. W. et al., (1992), Nuc. Acids Res., 20:2603), but sometimes as many as five bromodomain motifs (Nicolas, R. H. and Goodwin, G. H. (1996), Gene, 175 (12):233-240). This motif is found in a wide variety of animals. For example, it is identified in yeast (Winston, F. et al., (1987), Genetics, 115:649-656; Laurent, B. C. et al., (1991), Proc. Natl. Acad. Sci. USA, 88:2687-2691), in Drosophila (Digan, M. E. et al., (1986), Dev. Biol., 114:161-169; Tamkun, J. W. et al., (1992), Cell, 68:561-572), and in the genes for transcriptional regulators in mammals (Denis, G. V. and Green, M. R. (1996), Genes and Devel., 10:261-271; Yang, X. J. et al., (1996), Nature, 382:319-324).

[0004] All transcriptional regulators containing a bromodomain serve to control signal-dependent transcription in actively proliferating cells (Tamkun, J. W. et al., (1992), Cell, 68:561-572; Haynes, S. R. et al., (1992), Nuc. Acids Res., 20:2603). Due to this feature of these transcriptional regulators, it is suggested that cancer may develop if the gene for the protein containing a bromodomain is not normally controlled. In fact, several studies have shown that human transcriptional regulators with a bromodomain RING3, p300/CBP, and PCAF may be involved in oncogenesis.

[0005] RING3 is a transcriptional regulator highly homologous with the fsh protein that regulates development of Drosophila (Haynes, S. R. et al., (1989), Dev. Biol., 134:246-257). RING3 is a nuclear serine/threonine kinase having autophosphorylating activity. This activity of RING3 correlates with a proliferating state in chronic or acute lymphocytic leukemia. For instance, when Denis and Green collected lymphocytes of peripheral blood from 10 patients suffering from leukemia, kinase activity associated with RING3 was identified in all of the 10 patients but not in normal controls (Denis, G. V. and Green, M. R. (1996), Genes and Develop., 10:261-271). Furthermore, this activity was not detected in the blood cells from patients whose leukemia had remitted by virtue of chemotherapy.

[0006] p300 and CBP (CREB binding protein) encode highly similar proteins and are thus often called p300/CBP. p300/CBP is a co-activator for a transcriptional regulator CREB (cAMP responsive element binding protein) (Kwok, RPS et al., (1994), Nature, 370:223-226), and is considered as a key protein for growth regulation. Mutation in p300/CBP has been found in familial or sporadic cancers. Germline mutation of CBP results in Rubinstein-Taybi syndrome, which causes patients to develop various malignant tumors (Petrij, F. et al., (1995), Nature, 376:348-51), while mutation in p300 is found in sporadic colorectal and gastric cancers (Muraoka, M. et al., (1996), Oncogene, 12:1565-1569). Furthermore, CBP is fused with MOZ (Monocytic leukemia Zinc finger protein) in a t (8; 16) (p11; p13) translocation found in a certain kinds of acute myelocytic leukemia. The fusion protein has histone-acetyltransferase domains derived from both genes (Bannister, A. J. and Kouzarides, T. (1996), Nature, 384:641-643; Orgyzco, V. V. et al., (1996), Cell, 87:953-959; Brownwell, J. E. and Allis, C. D. (1996), Curr. Opin. Genet. Devel., 6:176-184). Since acetylated histone is known to be associated with transcriptionally active chromatin, the fusion protein may be involved in leukemogenesis by way of aberrant histone acetylation (Brownwell, J. E. and Allis, C. D. (1996), Curr. Opin. Genet. Devel., 6:176-184). p300/CBP is also considered to be associated with cancer since it interacts with known oncogene products. For example, p300/CBP binds to E1A protein (Arany, Z. et al.,(1995), Nature, 374:81-84), one of the early genes of adenovirus. p300 is also a co-activator for transcription factors, c-Myb (Dai, P. et al., (1996), Genes Dev., 10:528-540) and c-Fos (Bannister, A. J. and Kouzarides, T. (1996), Nature, 384:641-643).

[0007] PCAF, is considered to inhibit the interaction of E1A with p300/CBP by competing with E1A for binding to p300/CBP (Yang, X. J. et al., (1996), Nature, 382:319-324). PCAF also has histone-acetyltransferase activity.

[0008] Thus, it is thought that transcriptional regulators containing a bromodomain are involved in regulation of cell growth, and that their aberrant regulation may be closely related to various diseases, particularly to cancer. Transcriptional regulators containing a bromodomain have thus recently received much attention as novel targets for specifically treating cancer.

DISCLOSURE OF THE INVENTION

[0009] The objective of the present invention is to provide a novel transcriptional regulator containing a bromodomain and a gene encoding it, and a method of screening for a candidate compound as a medicament by using them.

[0010] As a result of research to achieve the above objective, the inventors successfully isolated several genes, each of which encodes a novel transcriptional regulator containing a bromodomain. The genes were isolated from a human testis cDNA library using primers designed based on EST sequences which had been identified using known bromodomain sequences as probes. In addition, the inventors have found that the structures of the isolated genes resemble one another, thus they constitute a family. The inventors have also found that the isolated genes or proteins encoded by them can be used to screen the candidate compounds for a medicament that controls the activity of the proteins or other factors interacting therewith.

[0011] Thus, the present invention relates to novel transcriptional regulators each having a bromodomain and the genes encoding them, and to a method of screening for a candidate compound as a medicament using said proteins or genes, and more specifically relates to:

[0012] (1) a transcriptional regulator having a bromodomain, which comprises the amino acid sequence shown in SEQ ID NO:1, 13, 21, 27, or 29, or said sequence wherein one or more amino acids are substituted, deleted, or added;

[0013] (2) a transcriptional regulator having a bromodomain, which is encoded by DNA hybridizing with DNA comprising the nucleotide sequence shown in SEQ ID NO:2, 14, 22, 28 or 30;

[0014] (3) DNA coding for the transcriptional regulator according to (1) or (2);

[0015] (4) a vector comprising the DNA according to (3);

[0016] (5) a transformant expressibly retaining the DNA according to (3);

[0017] (6) a method for producing the transcriptional regulator according to (1) or (2), which comprises culturing the transformant according to (5);

[0018] (7) an antibody binding to the transcriptional regulator according to (1) or (2);

[0019] (8) a method of screening a compound having binding activity to the transcriptional regulator according to (1) or (2), wherein the method comprises contacting a sample with the transcriptional regulator according to (1) or (2) and selecting a compound having binding activity to the transcriptional regulator according to (1) or (2);

[0020] (9) a compound having binding activity to the transcriptional regulator according to (1) or (2), which can be isolated according to the method of (8);

[0021] (10) the compound according to (9), which is naturally occurring; and

[0022] (11) DNA specifically hybridizing with DNA comprising the nucleotide sequence shown in SEQ ID NO:2, 14, 22, 28, or 30 and having at least 15 nucleotides.

[0023] Here, the term “transcriptional regulator(s)” means protein(s) that control gene expression, and “bromodomain” means an amino acid motif conserved among the transcriptional regulators associated with signal-dependent transcription, wherein said motif is involved in protein-protein interaction.

[0024] The present invention relates to novel transcriptional regulators having a bromodomain (BAZ family). The nucleotide sequences of cDNA isolated by the inventors, which belong to BAZ family, are shown in SEQ ID NO:2 (BAZ(BAZ1α)), SEQ ID NO:14 (BAZ2α), SEQ ID NO:22 (BAZ2β), and SEQ ID NO:28 and 30 (BAZ1β). The amino acid sequences of proteins encoded by the cDNA are also shown in SEQ ID NO:1 (BAZ(BAZ1α)), SEQ ID NO:13 (BAZ2α), SEQ ID NO:21 (BAZ2β), and SEQ ID NO:27 and 29 (BAZ1β).

[0025] The bromodomain is characteristic of a structural region that is conserved among a group of transcriptional regulators involved in signal-dependent transcription (Tamkun, J. W. et al., (1992), Cell, 68:561-572; Haynes, S. R. et al., (1992), Nuc. Acids Res., 20:2603), and it has been reported that the six mammalian genes, i.e., RING3, p300/CBP, PCAF, BRG1, HRX/ALL-1, and TIF1, which encode transcriptional regulators having a bromodomain, are associated with cancer. That the transcriptional regulators having a bromodomain are commonly associated with cancer suggests that the genes isolated by the inventors are also associated with cancer. Other than a bromodomain motif, the proteins encoded by the genes isolated by the inventors share the characteristic motifs of (1) C4HC3 zinc-finger, which is found in the proteins expressed in a wide range of organisms from yeast to human and is believed to be involved in a protein-protein interaction or nonspecific binding to DNA; (2) leucine zipper, which is present in many transcriptional regulators and is known to contribute to form a dimer with the protein itself or other proteins (Busch, S. J. and Sassone-Corsi, P. (1990), Trends in Genetics, 6:36-40); (3) LXXLL motif, a motif commonly found among many transcriptional co-activators, which is shown to be required for mediation of transcription induced by a nuclear receptor (Torchia, J. et al., (1997), Nature, 387:677-684; Heery, D. M. et al., (1997), Nature, 387:733-736); and (4) nuclear transport signal, which confers the transporting activity into the nucleus on the proteins synthesized in the cytoplasm.

[0026] The combination of a bromodomain and C4HC3 zinc finger is known to be associated with several breakpoint genes of leukemia (Tkachuk, D. C. et al., (1992), Cell, 71:691-700; Gu, Y. et al., (1992), Cell, 71:701-798; Miki, T. et al., (1991), Proc. Nat. Acad. Sci., 88:5167-5171; Le Douarin B. et al., (1995), EMBO J., 14:2020-2033; Borrow, J. et al., (1996), Nature Genet., 14:33-41). Accordingly, the genes isolated by the inventors are important candidates for breakpoint genes of cancers.

[0027] The transcriptional regulators of the present invention can be prepared as recombinant proteins generated using a recombinant gene technique, or as naturally occurring proteins, according to a method known to one skilled in the art. The recombinant proteins can be prepared using a method such as incorporating DNA encoding a transcriptional regulator of the present invention (e.g., DNA having the nucleotide sequence shown in SEQ ID NO:2, 14, 22, 28, or 30) into a suitable expression vector, which is then introduced into host cells, and purifying the protein obtained from the transformant. The naturally occurring proteins can be prepared using a method such as preparing a column which utilizes an antibody obtained from a small animal immunized with the recombinant protein prepared as above, and subjecting the extract from a tissue or cells in which a transcriptional regulator of the present invention is overexpressed (e.g., testis and cancer cells) to affinity chromatography using said column.

[0028] The present invention also relates to transcriptional regulators functionally equivalent to the transcriptional regulators of the present invention having the amino acid sequence shown in SEQ ID NO:1, 13, 21, 27, or 29. A method of introducing mutation into amino acids of a protein to isolate a protein functionally equivalent to a particular protein is well known to one skilled in the art. Thus, it is well within the art of an ordinarily skilled person to isolate a transcriptional regulator functionally equivalent to the transcriptional regulators of the present invention having the amino acid sequence shown in SEQ ID NO:1, 13, 21, 27, or 29 by appropriately modifying, for example, substituting amino acids without affecting the function of the transcriptional regulator. Mutation in an amino acid of a protein can also occur spontaneously. The transcriptional regulators of the present invention include those having a bromodomain and the amino acid sequence of SEQ ID NO:1, 13, 21, 27, or 29 wherein one or more amino acids are substituted, deleted, or added. Examples of known methods for introducing amino acid mutation into the protein are a site-directed mutagenesis system using PCR (GIBCO-BRL, Gaithersburg, Md.) and a site-directed mutagenesis using oligonucleotides (Kramer, W. and Fritz, H. J. (1987), Methods in Enzymol., 154:350-367). The number of mutagenized amino acids is usually 50 amino acids or less, preferably 30 amino acids or less, more preferably 10 amino acids or less, and most preferably three amino acids or less.

[0029] As another method of isolating a functionally equivalent protein utilizing a hybridization technique (Sambrook, J. et al., Molecular Cloning 2nd ed. 9.47-9.58, Cold Spring Harbor Lab. press, 1989) is well known to one skilled in the art. Based on the DNA sequence encoding the transcriptional regulator of the present invention shown in SEQ ID NO:2, 14, 22, 28, or 30, or the fragment thereof, a person with ordinary skill in the art can isolate DNA highly homologous to said DNA sequences using a hybridization technique (Sambrook, J. et al., Molecular Cloning 2nd ed. 9.47-9.58, Cold Spring Harbor Lab. press, 1989) to obtain a transcriptional regulator functionally equivalent to the transcriptional regulators. The transcriptional regulators of the present invention include those encoded by DNA that hybridizes with DNA comprising the DNA sequence shown in SEQ ID NO:2, 14, 22, 28, or 30, and which contains a bromodomain. The hybridization and washing conditions for isolating DNA encoding a functionally equivalent protein are defined as low stringency: 42° C., 2×SSC, 0.1% SDS; moderate stringency: 50° C., 2×SSC, 0.1% SDS; and high stringency: 65° C., 2×SSC, 0.1% SDS. The transcriptional regulators obtained by the hybridization technique may have amino acid homology of preferably 40% or more, more preferably 60% or more, still more preferably 80% or more, or most preferably 95% or more, with the transcriptional regulators having the amino acid sequence shown in SEQ ID NO:1, 13, 21, 27, or 29. In particular, high homology in the bromodomain sequence is considered significant for the function associated with cancer. Functionally equivalent transcriptional regulators to be isolated may contain, other than a bromodomain, a sequence involved in interaction with another protein (e.g., leucine-zipper or LXXLL motif), a sequence involved in binding to DNA (e.g. zinc finger), or a nuclear transport signal. The presence of the bromodomain in the protein can be identified by searching the bromodomain motif PROSITE database on DNASIS (HITACHI Software engineering).

[0030] The present invention also relates to DNA that codes for a transcriptional regulator of the present invention. The DNA of the present invention includes cDNA, genomic DNA, and chemically synthesized DNA, but is not limited thereto as long as it codes for a transcriptional regulator of the present invention. cDNA can be prepared, for example, by designing a primer based on the nucleic acid sequence shown in SEQ ID NO:2, 14, 22, 28, or 30 and performing plaque PCR (see Affara, N. A. et al., (1994), Genomics, 22:205-210). The genomic DNA can be prepared according to a standard technique using, for example, Qiagen genomic DNA kits (Qiagen, Hilden, Germany). The DNA sequence thus obtained can be determined according to a standard technique using a commercially available dye terminator sequencing kit (Applied Biosystems) and the like. In addition to applying to the production of recombinant proteins as described below, the DNA of the present invention may be applied to gene therapy and the like.

[0031] The present invention also relates to a vector into which the DNA of the present invention is inserted. There is no particular limitations to the vector into which the DNA of the present invention is inserted, and various types of vectors, e.g. for expressing the transcriptional regulators of the present invention in vivo and for preparing recombinant proteins, may be used for each purpose. Vectors used for expressing the transcriptional regulators of the present invention in vivo (in particular, for gene therapy) include the adenovirus vector pAdexLcw and the retrovirus vector pZIPneo. A LacSwitch II expression system (Stratagene; La Jolla, Calif.) is advantageous when mammalian cells, such as CHO, COS, and NIH3T3 cells, are used. An expression vector is particularly useful for producing a transcriptional regulator of the present invention. Although there is no particular limitation to the expression vectors, the following vectors are preferred: pREP4 (Qiagen, Hilden, Germany) when E. coli is used; SP-Q01 (Stratagene, La Jolla, Calif.) when yeast is used; and BAC-to-BAC baculovirus expression system (GIBCO-BRL, Gaithersburg, Md.) when insect cells are used. The DNA of the present invention can be inserted into vectors using a standard method.

[0032] The present invention also relates to a transformant expressibly retaining the DNA of the present invention. The transformants of the present invention include one harboring the above-described vector into which the DNA of the present invention is inserted and one having the DNA of the present invention integrated into its genome. The DNA of the present invention can be retained in the transformant in any form as long as the transformant expressibly retains the DNA of the present invention. There is no limitation to host cells into which a vector of the present invention is introduced. If the cells are used to express a transcriptional regulator of the present invention in vivo, desired cells may be used as target cells. Cells such as E. coli, yeast cells, animal cells, and insect cells can be used for producing the transcriptional regulators of the present invention. The vector can be introduced into the cells by methods such as electroporation and heat shock. Recombinant proteins can be isolated and purified from the transformants generated for producing the said proteins according to a standard method.

[0033] The present invention also relates to antibodies that bind to the transcriptional regulators of the present invention. The antibodies of the present invention include, but are not limited to, polyclonal and monoclonal antibodies. Also included are antisera obtained by immunizing an animal such as a rabbit with a transcriptional regulator of the present invention, any class of polyclonal or monoclonal antibodies, humanized antibodies generated by gene recombination, and human antibodies. The antibodies of the present invention can be prepared according to the following method. For polyclonal antibodies, antisera can be obtained by immunizing a small animal, such as a rabbit, with a transcriptional regulator of the present invention, then recovering the fractions that only recognize the transcriptional regulator of the present invention through an affinity column coupled with the transcriptional regulator of the present invention. Immunoglobulin G or M can be prepared by purifying the fractions through a Protein A or G column. For monoclonal antibodies, a small animal, such as a mouse, is immunized with a transcriptional regulator of the invention, the spleen is removed from the mouse and homogenized into cells, the cells are fused with myeloma cells from a mouse using a reagent such as polyethylene glycol, and clones that produce antibodies against the transcriptional regulator of the invention are selected from the resulting fused cells (hybridoma). The hybridoma obtained is then transplanted into the abdominal cavity of a mouse, and the ascites are recovered from the mouse. The obtained monoclonal antibodies can then be prepared by purifying, for example, by ammonium sulfate precipitation through a Protein A or G column, by DEAE ion exchanging chromatography, or through an affinity column coupled with the transcriptional regulator of the invention. Besides being used to purify or detect the transcriptional regulators of the present invention, the antiobodies of the present invention can be applied to antibody therapy.

[0034] The present invention also relates to a screening method for a compound that binds to transcriptional regulators of the present invention. The screening method of the present invention includes steps of contacting a transcriptional regulator of the present invention with a test sample and selecting a compound that has binding activity for the transcriptional regulator of the present invention. Test samples used for the screening include, but are not limited to, a cell extract, a supernatant of the cell culture, a library of synthetic low molecular weight compounds, a purified protein, an expression product of a gene library, and a library of synthetic peptides. Methods well known to one skilled in the art for isolating a compound binding to a transcriptional regulator of the present invention using the regulator are as follows. A protein that binds to a transcriptional regulator of the present invention can be screened by West-western blotting comprising steps of generating a cDNA library from the cells expected to express the protein that binds to a transcriptional regulator of the present invention (e.g., testis tissue cell and tumor cell lines HL-60, HeLa S3, Raji, and SW480) using a phage vector (λgt11, ZAP, etc.), allowing the cDNA library to express on the LB-agarose plate, fixing the expressed proteins on a filter, reacting them with the transcriptional regulator of the present invention purified as a biotin-labeled protein or a fusion protein with GST protein, and detecting plaques expressing the protein bound to the regulator on the filter with streptavidin or anti-GST antibody (Skolnik, E. Y., Margolis, B., Mohammadi, M., Lowenstein, E., Fisher, R., Drepps, A., Ullrich, A. and Schlessinger, J. (1991), Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases, Cell, 65:83-90). Alternatively, the method comprises expressing in yeast cells a transcriptional regulator of the present invention which is fused with SFR or GAL4 binding region, constructing a cDNA library in which proteins are expressed in a fusion protein with the transcription activation site of VP16 or GAL4 from the cells expected to express a protein that binds to the transcriptional regulator of the present invention, introducing the cDNA library into the above-described yeast cells, isolating the cDNA derived from the library from the detected positive clones, and introducing and expressing it in E. coli. (If a protein that binds to the transcriptional regulator of the present invention is expressed, a reporter gene is activated by the binding of the two proteins. The positive clones can then be identified.) This method can be performed using Two-hybrid system (MATCHMAKER Two-Hybrid System, Mammalian MATCHMAKER Two-Hybrid Assay Kit, MATCHMAKER One-Hybrid System (all from Clontech); HybriZAP Two-Hybrid Vector System (Stratagene) or in accordance with Dalton, S. and Treisman R. (1992), Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element, Cell, 68:597-612). Another method is to apply a culture supernatant or a cell extract from the cells suspected to express a protein which binds to the transcriptional regulator of the present invention onto an affinity column coupled with the transcriptional regulator of the present invention, and purify the protein specifically bound to the column.

[0035] Also well known to one skilled in the art are a method of screening molecules that bind to a transcriptional regulator of the present invention by reacting the immobilized transcriptional regulator of present invention with a synthetic compound, natural substance bank, or a random phage peptide display library, and a method of screening low molecular weight compounds, proteins (or their genes), or peptides which bind to a transcriptional regulator of the present invention by utilizing the high-throughput technique of combinatorial chemistry (Wrighton, N. C., Farrell, F. X., Chang, R., Kashuyap, A. K., Barbone, F. P., Mulcahy, L. S., Johnson, D. L., Barrett, R. W., Jolliffe, L. K., Dower, W. J., Small peptides as potent mimetics of the protein hormone erythropoietin, Science (UNITED STATES) Jul. 26, 1996, 273:458-464; Verdine, G. L., The combinatorial chemistry of nature, Nature (ENGLAND), Nov. 7, 1996, 384:11-13; Hogan, J. C. Jr., Directed combinatorial chemistry, Nature (ENGLAND), Nov. 7, 1996, 384:17-19). The compounds thus isolated, which bind to a transcriptional regulator of the present invention, may be used to treat cancer or other proliferative diseases. When the compounds isolated by the screening method of the present invention are used as pharmaceuticals, they can be formulated by a known pharmacological process. For example, they can be administered to a patient with pharmaceutically acceptable carriers and vehicles (e.g., physiological saline, vegetable oil, a dispersant, a surfactant, and a stabilizer). The compounds may be percutaneously, intranasally, transbronchially, intramuscularly, intravenously, or orally administered, depending on their properties.

[0036] The present invention also relates to DNA specifically hybridizing with DNA coding a protein of the present invention and having at least 15 nucleotides. As used herein, “specifically hybridizing” means that no cross-hybridization occurs between DNA encoding other proteins under conditions of moderate stringency. Such DNA may be used as a probe for detecting and isolating the DNA encoding the protein of the present invention, and as a primer for amplifying the DNA encoding the protein of the present invention.

[0037] An “isolated nucleic acid” is a nucleic acid the structure of which is not identical to that of any naturally occurring nucleic acid or to that of any fragment of a naturally occurring genomic nucleic acid spanning more than three separate genes. The term therefore covers, for example, (a) a DNA which has the sequence of part of a naturally occurring genomic DNA molecule but is not flanked by both of the coding sequences that flank that part of the molecule in the genome of the organism in which it naturally occurs; (b) a nucleic acid incorporated into a vector or into the genomic DNA of a prokaryote or eukaryote in a manner such that the resulting molecule is not identical to any naturally occurring vector or genomic DNA; (c) a separate molecule such as a cDNA, a genomic fragment, a fragment produced by polymerase chain reaction (PCR), or a restriction fragment; and (d) a recombinant nucleotide sequence that is part of a hybrid gene, i.e., a gene encoding a fusion protein. Specifically excluded from this definition are nucleic acids present in mixtures of different (i) DNA molecules, (ii) transfected cells, and (iii) cell clones: e.g., as these occur in a DNA library such as a cDNA or genomic DNA library.

[0038] The term “substantially pure” as used herein in reference to a given polypeptide means that the polypeptide is substantially free from other biological compounds, such as those in cellular material, viral material, or culture medium, with which the polypeptide was associated (e.g., in the course of production by recombinant DNA techniques or before purification from a natural biological source). The substantially pure polypeptide is at least 75% (e.g., at least 80, 85, 95, or 99%) pure by dry weight. Purity can be measured by any appropriate standard method, for example, by column chromatography, polyacrylamide gel electrophoresis, or HPLC analysis.

[0039] A “conservative amino acid substitution” is one in which an amino acid residue is replaced with another residue having a chemically similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine).

[0040] As used herein, “percent identity” of two amino acid sequences or of two nucleic acids is determined using the algorithm of Karlin and Altschul (Proc. Natl. Acad. Sci. USA 87:2264-2268, 1990), modified as in Karlin and Altschul (Proc. Natl. Acad. Sci. USA 90:5873-5877, 1993). Such an algorithm is incorporated into the NBLAST and XBLAST programs of Altschul et al. (J. Mol. Biol. 215:403-410, 1990). BLAST nucleotide searches are performed with the NBLAST program, score=100, wordlength=12 to obtain nucleotide sequences homologous to a nucleic acid molecules of the invention. BLAST protein searches are performed with the XBLAST program, score=50, wordlength=3 to obtain amino acid sequences homologous to a reference polypeptide. To obtain gapped alignments for comparison purposes, Gapped BLAST is utilized as described in Altschul et al. (Nucleic Acids Res. 25:3389-3402, 1997). When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) are used. See http://www.ncbi.nlm.nih.gov.

[0041] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present application, including definitions, will control. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference. The materials, methods, and examples are illustrative only and not intended to be limiting. Other features and advantages of the invention will be apparent from the detailed description, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0042]FIG. 1 compares the domain of BAZ (BAZ1α) with those of other proteins. In FIG. 1A, the bromodomain of BAZ (BAZ1α) is compared with that of TFIID from yeast, CCG1 from human, p300, and CBP. In FIG. 1B, C4HC3 Zn finger of BAZ (BAZ1α) is compared with those of U13646, retinoblastoma binding protein RBP2, two species of MOZ, p300, and CBP. The conserved amino acids, cysteine and histidine, are indicated by “*.” In both FIGS. 1A and B, identical amino acids are represented by reverse-contrast letters, and similar amino acids are represented by emphasized letters (also netted).

[0043]FIG. 2 shows a chromosome map of BAZ (BAZ1α). FIG. 2A shows assignments of chromosome 14 based on the analysis of a monochromosome hybrid cell panel using primers B (SEQ ID NO:6) and M (SEQ ID NO:7). The numbers 1 to Y in the figure refer to chromosome numbers, and TH refers to total human chromosomes. The 111 bp product was specifically amplified in the cell line GM10479, monochromosomel for a human chromosome 14. FIG. 2B depicts the location of BAZ (BAZ1α) on chromosome 14 as determined by Genebridge 4 radiation hybrid panel analysis.

[0044]FIG. 3 shows the expression of BAZ (BAZ1α) in normal tissues (Lane 1, heart; Lane 2, brain; Lane 3, placenta; Lane 4, lung; Lane 5, liver; Lane 6, skeletal muscle; Lane 7, kidney; Lane 8, pancreas; Lane 9, spleen; Lane 10, thymus; Lane 11, prostate; Lane 12, testis; Lane 13, ovary; Lane 14, small intestine; Lane 15, colon (mucous lining); and Lane 16, leukocytes in the peripheral blood). The bottom of the figure shows control bands using actin probes.

[0045]FIG. 4 shows the expression of BAZ (BAZ1α) in carcinoma. FIG. 4A depicts the Northern blot analysis in the carcinoma cell lines (Lane 1, promyelocytic leukemia HL-60; Lane 2, HeLa S3 cells; Lane 3, chronic myelocytic leukemia K-562; Lane 4, lymphoblastic leukemia MOLT-4; Lane 5, Burkitt's lymphoma Raji; Lane 6, large intestine adenocarcinoma SW480; Lane 7, lung carcinoma A549; and Lane 8, melanoma G361). FIG. 4B shows the RT-PCR analysis of primary lung carcinoma of Lane 10. The top panel shows the amplified product of 554 bp from BAZ (BAZ1α) gene using primers U and N, and the bottom shows the amplified product of 442 bp from G3PDH gene using primers G3U and G3L. In the figures, L refers to normal human lung; T, to normal human testis; and G, to normal human genomic DNA.

[0046]FIG. 5 compares the conserved domains among BAZ (BAZ1α), BAZ2α, and U13646.

[0047]FIG. 6 shows alignments of the domain of BAZ2α and that of other proteins. In FIG. 6A, the bromodomain of BAZ2α (BAZ2 in the figure) is aligned with BAZ (BAZ1α) human CCG1, PCAF, and CBP. In FIG. 6B, C4HC3 Zn finger of BAZ2α is aligned with BAZ (BAZ1α), U13646, retinoblastoma binding protein RBP2, 2 zinc fingers of MOZ, and p300. The conserved cysteine and histidine are indicated by “*.”

[0048]FIG. 7 shows a chromosome map of BAZ2α. FIG. 7A shows assignments of chromosome 12 based on the analysis of a monochromosome hybrid cell panel using primers D (SEQ ID NO:16) and E (SEQ ID NO:17). The numbers 1 to Y in the figure refer to chromosome numbers. The product of 132 bp was specifically amplified in the cell line GM10868a, a monochromosome for human chromosome 12. FIG. 7B depicts the location of BAZ2 (BAZ2α) on chromosome 12 as determined by Genebridge 4 radiation hybrid panel analysis.

[0049]FIG. 8 shows the expression of BAZ2α in normal tissues (A: Lane 1, heart; Lane 2, brain; Lane 3, placenta; Lane 4, lung; Lane 5, liver; Lane 6, skeletal muscle; Lane 7, kidney; Lane 8, pancreas; Lane 9, spleen; Lane 10, thymus; Lane 11, prostate; Lane 12, testis; Lane 13, uterus; Lane 14, small intestine; Lane 15, colon (mucous lining); and Lane 16, leukocytes in the peripheral blood). FIG. 8B shows controls using actin probe.

[0050]FIG. 9 compares the conserved domains of BAZ2α, BAZ1α, BAZ2α, U13646, and BAZ1βS. Each has at least five domains. BAZ1α lacks domain I. The figures on the bars of BAZ2β, BAZ1α, U13646, and BAZ1βS represent the percentage of the homology with BAZ2α. The values in the LH domain represent the percentage of the homology with leucine residues. Black bands in the LH domain indicate where the LXXLL motif is present in all three BAZ genes. LH, ZF, and BD represent leucine-rich helix domain, C4HC3 zinc finger, and bromodomain, respectively.

[0051]FIG. 10 compares the amino acid sequence of LH domain in BAZ2β with those of corresponding domains in other proteins. The positions of conserved leucine residues are indicated by arrows on the sequences. LXXLL motifs are boxed.

[0052]FIG. 11 shows a chromosome map of BAZ2β. The product of 147 bp was specifically amplified in the cell line as a monochromosome for human chromosome 2. This product was amplified by PCR using primers nb7n and nb7ee. The numbers 1 to Y in the figure indicate chromosome numbers. The location of BAZ2β on chromosome 2 was determined by Genebridge 4 radiation hybrid panel analysis.

[0053]FIG. 12 shows an analysis of the expression of BAZ2β in normal tissues, carcinoma cell lines, and fetal tissues (Lane 1, heart; Lane 2, brain; Lane 3, placenta; Lane 4, lung; Lane 5, liver; Lane 6, skeletal muscle; Lane 7, kidney; Lane 8, pancreas; Lane 9, spleen; Lane 10, thymus; Lane 11, prostate; Lane 12, testis; Lane 13, uterus; Lane 14, small intestine; Lane 15, colon (mucous lining); Lane 16, leukocytes in the peripheral blood; Lane 17, fetal brain; Lane 18, fetal lung; Lane 19, fetal liver; Lane 20, fetal kidney; Lane 21, acute leukemia HL-60; Lane 22, HeLa S3 cells; Lane 23, chronic myelocytic leukemia K-562; Lane 24, lymphoblastic leukemia MOLT-4; Lane 25, Burkitt's lymphoma Raji; Lane 26, large intestine adenocarcinoma SW480; Lane 27, lung carcinoma A549; and Lane 28, melanoma G361). The sizes of the transcripts are indicated on the right side of the figure.

[0054]FIG. 13 shows the alignments of variable portions of BAZ1βS and BAZ1βL.

[0055]FIG. 14 shows the alignments of N terminal amino acid sequences from BAZ1βS and three other members of the BAZ family. The residues with 50% or more sequence homology are indicated by dark shadowed boxes, and those with 50% or more sequence similarity, by light shadowed boxes. Conserved LXXLL motifs and C4HC3 zinc fingers are indicated on the alignments. Conserved leucine residues in the surrounding region of the LXXLL motif are indicated. The location of a bromodomain motif is indicated by a black line on the alignments.

[0056]FIG. 15 shows the alignments of the amino acid sequences from BAZ1βS and three other members of the BAZ family (continued from FIG. 14).

[0057]FIG. 16 shows the alignments of the amino acid sequences from BAZ1βS and three other members of the BAZ family (continued from FIG. 15.

[0058]FIG. 17 shows the alignments of the amino acid sequences from BAZ1βS and three other members of the BAZ family (continued from FIG. 16).

[0059]FIG. 18 shows the alignments of the amino acid sequences from BAZ1βS and three other members of the BAZ family (continued from FIG. 17).

[0060]FIG. 19 shows a chromosome map of BAZ1β. FIG. 19A shows mapping of BAZ1β on chromosome seven by monochromosome hybrid cell line panel analysis. A product of 156 bp was observed to be amplified in the cell line GM10791 by PCR using primers nb3S and nb3T. The numbers 1 to Y in the figure indicate chromosome numbers. FIG. 19B shows the location of BAZ1β on chromosome seven as determined by Genebridge 4 radiation hybrid panel analysis. BAZ1β is located between 7q11-21 markers D7S489 and D7S669.

[0061]FIG. 20 shows the expression analysis of BAZ1β in normal tissues. In FIG. 20A, the BAZ1β probe is hybridized with two transcripts in a wide range of tissues (Lane 1, heart; Lane 2, brain; Lane 3, placenta; Lane 4, lung; Lane 5, liver; Lane 6, skeletal muscle; Lane 7, kidney; Lane 8, pancreas; Lane 9, spleen; Lane 10, thymus; Lane 11, prostate; Lane 12, testis; Lane 13, uterus; Lane 14, small intestine; Lane 15, colon (mucous lining); and Lane 16, leukocytes in the peripheral blood). FIG. 20B shows controls using an actin probe. In FIG. 20B, the blot in FIG. 20A was used to rehybridize with the actin probe.

[0062]FIG. 21 shows the regions within BAZ2β which are covered by expression clones. Conserved domains (shadowed boxes) and LXXLL motifs (black lines) are indicated. Positions of the first and the last amino acids of each domain are indicated on the bar. Clone 1 covers amino acids 1-190; clone 9, amino acids 1241-1584; and clone 11, amino acids 1500-1970.

[0063]FIG. 22 is a photograph of electrophoretic patterns showing SDS-PAGE analysis of GST protein (Lane 1, cell lysate (BAZ2β.1); Lane 2, flow through fraction (BAZ2β.1); Lane 3, purified fusion protein (BAZ2β.1); Lane 4, cell lysate (BAZ2β.11); Lane 5, cell lysate (BAZ2β.9); Lane 6, flow through fraction (BAZ2β.11); Lane 7, flow through fraction (BAZ2β.9); Lane 8, purified protein (BAZ2β.11); and Lane 9, purified protein (BAZ2β.9). The positions of molecular weight markers are indicated on the right (kDa).

[0064]FIG. 23 is a photograph of electrophoresis showing Western analysis of purified GST-fusion protein (Lane 1, GST; Lane 2, GST-BAZ2β.1; Lane 3, GST-BAZ2β.9; and Lane 4, GST-BAZ2β.11).

BEST MODE FOR IMPLEMENTING THE INVENTION

[0065] The present invention is further illustrated with reference to the following examples, but is not to be construed to be limited thereto.

EXAMPLE 1 Isolation and Analysis of BAZ Gene

[0066] (1) Identification of Novel Genes each Containing a Bromodomain

[0067] The EST database was searched by means of BLAST using the DNA sequence that encodes the 5′ bromodomain motif of the RING3 gene (SEQ ID NO:3) (Beck, S. et al., (1992), DNA Sequence, 2:203-210), and a number of ESTs identical to the probe sequence were retrieved. The following experiment was then performed for one of those EST, H70181. H70181 has the highest homology to transcription activator GCN5 of yeast (Georgakopoulos, T. and Thireos, G. (1992), EMBO J., 11(11):4145-4152) or human (Candau, R. et al., (1996), Mol. Cell. Biol., 16(2):593-602).

[0068] (2) Isolation of a Full-Length Sequence

[0069] To clone a full-length sequence of EST H70181, PCR primers were designed; primer U, SEQ ID NO:4/AGAAAAAGACAATCTCCAGAGCA, and primer L, SEQ ID NO:5/GCTGTCATCATGTCGTACCAATTC. The specific product of 129 bp obtained from testis cDNA was amplified by RT-PCR using said primers. The amplified product was directly purified through a QIA Quick (Qiagen) purification column. This PCR product was used as a probe for screening the testis cDNA library (Clontech; HL3023a). The probe was labeled with [α-³²P]dCTP by random priming, and purified using a Chromaspin 10 Column (Clontech); the cDNA clone obtained was used to re-screen the library. This process was repeated until a series of overlapped clones was obtained, and thus a full-length sequence was obtained. The isolated sequence was 5,934 bp in total. The isolated gene was designated “BAZ” (Bromodomain, Atypical Zinc finger). BAZ has an open reading frame (ORF) (SEQ ID NO:1) coding for 1,674 amino acids from the nucleotide positions 125-5147. The ORF is followed by 787 bp of a 3′ untranslated region and terminated with a poly-A tail. The polyadenylation signal (AATAAA) is located at 21 bp upstream from the poly-A tail. The nucleotide sequence together with the deduceded amino acid sequence therefrom is shown in SEQ ID NO:2.

[0070] The filter screening of the library was performed in ExpressHyb hybridization solution (Clontech) at 65° C. for 1 hour. The filter was then washed until a final stringency of 1×SSC and 0.1% SDS at 65° C. was attained. All the sequencing was performed on automated sequencing apparatus ABI 377 (Perkin Elmer, Norwalk, Conn.), utilizing ABI dye terminator chemistry.

[0071] (3) Identification of the Homology and Motifs Characterizing the Transcription Factors

[0072] A protein database search using the amino acid sequence of BAZ revealed that a protein encoded by a continuous 2.2 Mb gene sequence of the chromosome III of C. Eelegans (Wilson, R. et al., (1994), Nature, 368:32-38) is most similar (46% similarity and 23% identity). The same regions having similarity were found in various transcription factors such as the 250 KD subunit of TFIID (Ruppert, S., Wang, E., and Tjian, R. (1993), Nature 362:175-179) and p300/CBP (Eckner, R. et al., (1994), Genes Dev., 8(8):869-884; Chrivia, J. C. et al., (1993), Nature, 365:855-859). A motif search of amino acid sequences in the PROSITE database on DNASIS (HITACHI Software Engineering Co.) identified a single bromodomain (amino acid residues 1569-1627 of SEQ ID NO:1). The sequence of this bromodomain, together with those of other bromodomains, is shown in FIG. 1A. A BLAST search using C4HC3 Zn finger (C4HC3ZF), which is the motif conserved among a great variety of proteins such as U13646, identified retinoblastoma binding protein RBP2 (Fattaey, A. R. et al., (1993), Oncogene, 8:3149-3156), MOZ (Borrow, J. et al., (1996), Nature Genet., 14:33-41), and p300/CBP (Koken, M. H. et al., (1995), CR Acad. Sci. III, 318:733-739), a motif of 45 amino acids (corresponding to amino acid residues 1269-1313 of SEQ ID NO:1). C4HC3ZFs present in these genes are shown in FIG. 1B. The function of BAZ as a transcriptional regulator is implied by the fact that it is similar to several transcriptional regulators, in particular, a bromodomain motif conserved together with C4HC3ZF and p300/CBP. The similarity of BAZ to p300/CBP is not limited to C4HC3 zinc finger and bromodomain regions; well conserved regions are also found adjacent to the bromodomain. Homology was not found between BAZ and histone-acetyltransferase domain, and between BAZ and other domains in which p300/CBP is present. However, BAZ potentially has HAT activity since the histone-acetyltransferase domain is not well conserved among proteins.

[0073] Several sorts of sequence motifs characterized by the nuclear proteins were identified at 11 sites by employing the PSORT program (http://psort.nibb.ac.jp) utilizing a wide variety of conserved nuclear localization sequences.

[0074] (4) Mapping of BAZ

[0075] Primers B SEQ ID NO:6/AACACAAGTGAAGCAAAAGCTGGA and M SEQ ID NO:7/GTGGTGTGCTAACTTGGTCCACAT (obtained from the 3′ end of the gene) were used to amplify DNA obtained from each of the 24 monochromosomes of human/rodent somatic cell lines available from Coriell Cell Respositories, New Jersey (Dubois, B. L. and Naylor, S. (1993), Genomics, 16:315-319). The expected product of 111 bp was amplified only from GM10479, a monochromosomal cell line for human chromosome 14 (see FIG. 2A). Primers B (SEQ ID NO:6) and M (SEQ ID NO:7) were subsequently used for PCR onto a GeneBridge 4 radiation hybrid panel (Research Genetics, Huntsville, Ala.). The binary codes generated by assessing whether each hybrid is positive or negative for amplification were compared with the analogous codes for the markers constituting a framework map, using the server located at http://www-genome.wi.mit.edu./cgi-bin/contig/rhmapper.pl. This step was repeated using primers W: SEQ ID NO:8/CCCATCGTGAGTCAAGAGTGTCTGT and X: SEQ ID NO:9/CTCGCTTCTACCTTTTTATTGGCT (from the 5′ end of the gene). Based on the pattern obtained from this panel by identifying the amplification in the panel, BAZ was proved to be located on the 14q between the two markers D14S730 and D14S75 (see FIG. 2B).

[0076] (5) Analysis of BAZ Expression in the Normal Tissues

[0077] The probe as synthesized in Example 1(2) by amplifying cDNAs from testis with PCR using the above-described primers U (SEQ ID NO:4) and L (SEQ ID NO:5) was used for Northern blot analysis of 16 panels of normal tissues. The probe hybridized with a single species of mRNA of 7.0 kb, which corresponds to the length of the ORF identified from the sequence of the gene. Though this transcript was expressed in almost all the tissues at very low levels, it was expressed in testis at a relatively high level (see FIG. 3). The transcript was not detectable in brain, lung, liver, kidney, and colon (it was possibly expressed at non-detectable levels). A slightly smaller transcript of 6.5 kb was also detected only in testis at a low level. Since the cells divide more vigorously in the testis than any other tissue examined, the expression pattern is thought to correspond to the role for BAZ during active proliferation. Hybridization for Northern blot analysis was performed in Express Hyb hybridization solution (Clontech) at 65° C. for 1 hour. The filters were washed until the final stringency reached 1×SSC and 0.1% SDS at 65° C. Imaging was performed using a Fuji BAS Image Analyzer (Fuji Photo Film).

[0078] (6) Analysis of BAZ Expression in Tumor

[0079] That BAZ is highly expressed in the testis suggests the possibility of its high level expression in vigorously proliferating tumors. Thus, Northern analysis of eight panels of tumor cell lines was carried out, using the same probe as used in Example 1(5). As a result, the transcript of 7.0 kb alone was hybridized with the probe as when the normal tissue was used. Compared with most normal tissues, however, the transcriptional levels are remarkably higher in most of the tumor cell lines (see FIG. 4A). Specifically, the expression was higher in the tumor cell lines HL-60, HeLa S3, Raji, and SW480. In contrast, the expression levels in K-562, MOLT-4, A549, and G361 are almost the same as those in normal tissues.

[0080] RT-PCR was used to examine the expression of BAZ in the primary lung carcinomas as shown in Table 1. TABLE 1 Sample Patients No. age sex Carcinoma 1 49 male papillary adenocarcinoma 2 63 male papillary adenocarcinoma (moderately differentiated) 3 60 male papillary adenocarcinoma (poorly differentiated) 4 70 male squamous cell carcinoma (fusiform cell variant) 5 76 male papillary adenocarcinoma 6 65 male large lung cell carcinoma (moderately differntiated) 7 77 male squamous cell carcinoma (poorly differentiated) 8 45 male acinic adenocarcinoma 9 50 male carcinoid tumor 10 66 male choriocarcinoma

[0081] Each of the 10 samples was amplified using the primers G3U SEQ ID NO:10/TCATCATCTCTGCCCCCTCTGTCTG and G3L SEQ ID NO:11/GACGCCTGCTTCACCACCTTCTTG, which are the primers for amplifying 442 bp of a house-keeping gene G3PDH, and the primers U, SEQ ID NO:4 and N, SEQ ID NO:12/TCATGTGGTCAATCAATTGTTTGT, which are primers for BAZ (see FIG. 4). G3PDH was used to determine that an equal amount of mRNA was present in each sample.

[0082] The primers for BAZ were selected to specifically amplify the cDNA but not genomic DNA. The amplified product was definitely detected in the sample from the testis and the two lung tumors, but not from the other eight samples from the lung tumor or the normal lungs.

[0083] RT-PCR was performed according to a standard technique in which total RNA was extracted according to the AGPC method (Chomczynski, P. and Sacchi, N. (1987), Analytical Biochem., 162:156-159), then single-stranded DNA was synthesised with an oligo (dT15) primer and MMLV reverse transcriptase, a part of which was used for the RT-PCR. The RT-PCR was performed using AmpliTaq gold (ABI), with 27 cycles of annealing at 60° C. to amplify G3PDH and 33 cycles of annealing at 55° C. to amplify BAZ. The conditions for hybridization and imaging were the same as in Example 1(5).

EXAMPLE 2 Isolation and Analysis of BAZ2α Gene

[0084] (1) Identification of a Novel Gene Containing a Bromodomain and Isolation of its Full-Length Sequence

[0085] The DNA encoding the bromodomain of BAZ is highly homologous to that of GCN5. The DNA sequence encoding the bromodomain motif of human GCN5 gene (Candau, R. et al., (1996), Mol. Cell. Biol., 16 Q):593-602) was used to search the EST database using BLAST. The Motif search was performed using PROSITE. Proteins were compared using Bestfit in GCG. The nuclear transport signal was identified using PSORT. As a result, a number of ESTs were found to be identical to the probe sequence. Among them, an EST (Accession Number: N76552) obtained from a fetal liver/spleen cDNA library proved to be a novel gene.

[0086] To start cloning the full-length sequence of EST N76552, PCR primers were designed to amplify a particular product of 91 bp from the testis cDNA library; primer NB16U (SEQ ID NO:15/TGACTCTGAAGTAGGCAAGGCTGG) and primer NB16L (SEQ ID NO:16/CTTGCCTCACAGATTGGCCTGT). The PCR product was used as a probe to screen the testis cDNA library (Clontech; HL3023a). The amplified product was directly purified through a QIA Quick (Qiagen) purification column. The cDNA clone having sequences corresponding to EST was used to re-screen the library.

[0087] This process was repeated until a series of overlapped clones having a full-length sequence of the complete coding region was obtained. All the sequencing was performed with automated sequencing apparatus ABI 377 (Perkin Elmer, Norwalk, Conn.), utilizing ABI dye terminator chemistry. As a result, a continuous sequence consisting of 9,408 bp nucleotides in total size was generated. Theoretical translation of this sequence showed a presence of methionine codon at the nucleotide position of 740. An open reading frame (ORF) coding 1878 amino acids starts from this position and terminates at the nucleotide position 6373. The ORF is followed by a 3′ untranslated region consisting of at least a 3 kb nucleotide sequence. The nucleotide sequence of the cDNA obtained is shown in SEQ ID NO:14, and the amino acid sequence deduced from the cDNA is shown in SEQ ID NO:13. The isolated clone was designated BAZ2α.

[0088] (2) Identification of the Homology and Motifs Characteristic of Transcription Factors

[0089] Like BAZ, BAZ2α was shown to have the highest homology with the protein encoded by a C. elegans bromodomain gene U13646, the gene forming a part of a continuous 2.2 Mb segment of chromosome III of C. elegans (Wilson, R. et al., (1994), Nature, 368:32-38) by searching the protein databases with the amino acid sequence of BAZ2α. The regions which showed similarity were identified using various transcription factors such as the 250 KD subunit of TFIID (Ruppert, S., Wang, E. and Tjian, R. (1993), Nature 362:175-179) and p300/CBP (Eckner, R. et al., (1994), Genes Dev., 8(8):869-884; Chrivia, J. C. et al., (1993), Nature, 365:855-859). The bromodomain was located between the amino acid residues 1788 and 1846. The alignments of BAZ2α, BAZ, and U13646 are shown in FIG. 5. The alignments of the sequence of the BAZ2α bromodomain and those of other bromodomains are shown in FIG. 6A. Moreover, a single motif consisting of 45 amino acids (amino acid residues 1652-1696) was identified. This motif codes C4HC3 Zinc finger (C4HC3ZF), a motif conserved among a large number of proteins such as BAZ, U13646, retinoblastoma binding protein RBP2 (Fattaey, A. R. et al., (1993), Oncogene, 8:3149-3156), MOZ (Borrow, J. et al., (1996) Nature Genet., 14:33-41), and p300/CBP (Koken, M. H. et al., (1995) CR, 4 cad. Sci. III, 318:733-739) by BLAST searching. The alignments of C4HC3ZF from these genes are shown in FIG. 6B. BAZ2α resembles BAZ, which suggests the possibility that the two proteins closely relate and form a part of a protein family having a similar function. Like BAZ, BAZ2α wholly resembles several transcription factors and has C4HC3ZF and bromodomain motifs conserved among p300/CBP and TIF1, especially indicating that BAZ is likely to function as a transcriptional regulator.

[0090] An LXXLL motif, which is believed to be required for mediating transcription induced by nuclear receptors (Torchia, J. et al., (1997), Nature, 387:677-684; Herry, D. M. et al., (1997), Nature 387:733-736), is located at amino acid residue 872. PROSITE motif searching revealed that this motif was located at the 3′ end of the leucine zipper (amino acid residues 852-873). The relative locations of LXXLL, C4HC3, and bromodomain motifs in BAZ2α are remarkably similar to those of U13646 and BAZ (FIG. 5). Furthermore, in either case, the LXXLL motif is located behind the helix structure characterized by conserved lysine residues existing at regular intervals.

[0091] (3) Mapping of BAZ2α

[0092] To locate BAZ2α on the chromosome, PCR primers D (SEQ ID NO:17/TTGCCGTATTTGGCTGGTATC) and E (SEQ ID NO:18/CATAGAGAAGAGGGCAGGGTTGA), which amplify a fragment of 132 bp, were used to amplify the DNA from each of the 24 monochromosomes of human/rodent somatic cell lines (Dubois, B. L. and Naylor, S. (1993), Genomics, 16:315-319) obtained from Coriell Cell Respositories (New Jersey). The BAZ2α-containing region was identified using 91 GeneBridge 4 radiation hybrid panels (Walter M. A. et al., (1994), Nature Genetics, 7:22-28). These panels were screened by PCR using primers D and E again. The binary codes generated by assessing whether each hybrid is positive or negative for amplification were compared with the analogous codes for the markers constituting a framework map, using the server located at http://www-genome.wi.mit.edu/cgi-bin/contig/rhmapper.pl. BAZ2α was thus proved to be located 12q24.3-ter from D12S367(see FIG. 7B).

[0093] (4) Analysis of the BAZ2α Expression

[0094] The probe (a 481 bp fragment of BAZ2α gene) prepared by amplifying the DNA from one of the clones obtained from the testis cDNA library (Clontech) in Example 2(1) using primers gt10F (SEQ ID NO:19/CTTTTGAGCAAGTTCAGCCT) and NB16N (SEQ ID NO:20/GTCGGCTTCTTCATTTCCTCCA) was used for Northern analysis of 16 panels of normal tissues (Clontech). The probe was labeled with [α-³²P]dCTP by random priming and purified using a Chromaspin 10 column (Clontech). Hybridization for Northern analysis and library filter screening were performed in the ExpressHyb hybridization solution (Clontech) at 65° C. for 1 hour. The filters were then washed until the final stringency reached 0.5×SSC and 0.1% SDS. Imaging was performed using a Fuji BAS Image Analyzer. The result showed that this probe was hybridized with a single species of mRNA of 10.5 kb in almost all the tissues; this length corresponds to that of ORF identified from the gene sequence (FIG. 8). The transcript was expressed in almost all the tissues at a low level. Another transcript of 9.0 kb was-detected and was primarily expressed in the testis. This band survived the high-stringent wash. The second transcript is thought to be an alternatively spliced form of, or a different gene closely related to, BAZ2α.

EXAMPLE 3 Isolation and Analysis of BAZ2β Gene

[0095] (1) Identification of a Novel Gene Containing a Bromodomain and Isolation of Its Full-Length Sequence

[0096] A BLAST search was performed against the EST databases using the various nucleotide sequences containing a known bromodomain motif. Several ESTs which may encode the bromodomain gene were identified based on the result of the search using the nucleotide sequence of the SMAP gene (Nielsen, M. S. et al., (1996), Biochem. Biophys. Acta). Among them, an EST (Gnbank Accession Number: AA015589) obtained from a retinal cDNA library was proved to be a novel gene, the protein deduced from which has the highest homology with BAZ2α.

[0097] Its full-length nucleotide sequence was isolated. The full-length gene for EST AA015589 was cloned as follows. First, PCR primers NB7U (SEQ ID NO:23/CTGACTGAAATGGAAACTCATGAGG) and NB7L (SEQ ID NO:24/CTAGAGCAAAGGTTTCAAGGTTTGG) were designed to obtain the specific product of 165 bp from the testis cDNA. The amplified product was directly purified with a QIA Quick (Qiagen) purification column. The PCR product was used as a probe to screen the testis cDNA library, and the cDNA clone containing the EST sequence was used to re-screen the library. This process was repeated until the nucleotide sequence covering the whole coding region of the gene was obtained by assembling the clones. As a result, a nucleotide sequence consisting of 7,585 bp in total was obtained. This full-length sequence contains an open reading frame (ORF) consisting of 1972 amino acids (6,282 nucleotides) with ATG at the nucleotide position 367 as the initiation codon, followed by 3′ UTR of 1303 bp. SEQ ID NO:22 shows the nucleotide sequence of the cDNA thus obtained, and SEQ ID NO:21 shows the amino acid sequence deduced from the nucleotide sequence. All the sequencing was performed on automated sequencing apparatus ABI 377 (Perkin Elmer, Norwalk, Conn.), utilizing ABI dye terminator chemistry. Hybridization for the library filter screening was performed using ExpressHyb hybridization solution (Clontech) at 65° C. for 1 hour. The filters were washed until the final stringency reached 0.5×SSC and 0.1% SDS. Subsequently, the filters were subjected to autoradiography at −70° C. for 1 to 3 days to intensify their signals.

[0098] (2) Homology and the Characteristics of the Motifs of the Transcriptional Regulator

[0099] The motifs of the protein encoded by the gene obtained were searched for in PROSITE. The proteins were compared using Bestfit from GCG. A nuclear transport signal was identified through PSORT (http://psort.nibb.ac.jp/form.html).

[0100] As for BAZ and BAZ2α, a database search based on the amino acid sequences predicted from the registered genes showed that this gene has the greatest similarity to the protein encoded by the bromodomain gene U13646 from the nematode (C. elegans). This nematode bromodomaingene corresponds to a portion of a 2.2 Mb segment derived from chromosome III of the nematode (C. elegans) (Wilson, R. et al., (1994), Nature, 368:32-38). The gene, however, shows homology to BAZ and BAZ2α to a larger extent. Actually, the similarity of the protein encoded by this gene to BAZ and BAZ2α suggests the possibility that these three proteins are closely related to one another, and, moreover, that they are a part of a broader family of proteins with similar functions. This gene was designated BAZ2β (for bromodomain, a typical zinc finger), since it has the greatest association with BAZ2α. BAZ was also renamed BAZ1α. The amino acid sequence of BAZ2β is shown in FIG. 9 together with those of BAZ1α, BAZ2α, U13646, and BAZ1βS described below. At least five regions or domains can be identified from the sequences. The first domain (I) is not present in BAZ1α, but is in the other three proteins. The existence of a leucine-rich helical structure (LH) was predicted from the analysis of the next domain. LXXLL motif is present at the central part of this domain on all BAZs except U13646. This motif potentially confers the interaction with the nuclear receptors on the protein (Torchia, J. et al., (1997), Nature, 387:677-684; Heery, D. M. et al., (1997), Nature, 387:733-736). Both domains II and III are highly conserved, suggesting their functional importance. Each protein has a highly conserved C4HC3 zinc finger (Aasland, R. et al., (1995), Trends Biochem. Sci., 20:56-59; Koken, M. H. et al., (1995), CR Acad. Sci. III, 318:733-739; Saha, V. et al., (1995), Proc. Natl. Acad. Sci., 92:9737-9741) and a bromodomain. In addition, a conserved region is found upstream from the zinc-finger motif, and the region can also be functionally important. Similarly, there are conserved sequences upstream from the bromodomain motif. Such conserved domains are aligned in FIG. 10. Like BAZ1α and BAZ2α, BAZ2β exhibits great similarity to several transcription factors and is thus expected to function as a transcription factor. Consistent with this function, estimation of the protein localization in the cell using the PSORT program revealed that BAZ2β has 19 consensus nuclear localization sequences (Robbins, J. et al., (1991), Cell, 64:615-23) in total.

[0101] (3) Chromosomal Mapping of BAZ2β

[0102] To create a chromosome map of BAZ2β, primers nb7n (SEQ ID NO:25/TGTTGCTGCATCACTTGTGTAGTT) and NB7ee (SEQ ID NO:26/GGCATGACAATAATGTCTGCAAA) were prepared and used to amplify the DNA obtained from each of the 24 human/rodent monochromosomal somatic cell lines (Dubois, B. L. and Naylor, S. (1993), Genomics, 16:315-319). The amplification of the 147 bp fragment as expected PCR product indicated that the gene was likely to be located on human monochromosome 2 (FIG. 11). The locus region of BAZ2β was determined by use of 91 radiation hybrid panels of GeneBridge 4 (Walter, M. A. et al., (1994), Nature Genetics, 7:22-28). The hybrid panels were screened by PCR using primers nb7n and nb7ee again. The binary codes generated by assessing whether each hybrid is positive or negative for the amplification were compared with the analogous codes for the markers constituting a framework map, using the server located at http://www-genome.wi.mit.edu/cgi-bin/contig/rhmapper.pl to identify the chromosomal locus of this gene. As a result, BAZ2β was confirmed to be located on chromosome 2q23-24 and between markers D2S1986 and G09369 (FIG. 11).

[0103] (4) Analysis of the BAZ2β Expression

[0104] The cDNA probe containing the sequence correponding to nucleotide residues 1700-4000 was used for Northern analysis of 16 normal tissues, eight tumor cell lines, and four fetal tissues (FIG. 12). The probe was labeled with [α-³²P]dCTP by random priming and purified on a Chromaspin 10 column (Clontech). Hybridization for Northern analysis was performed at 65° C. for 1 hour using ExpressHyb hybridization solution (Clontech). Subsequently, the filters were washed at 65° C. until the final stringency reached 0.5×SSC and 0.1% SDS. Autoradiography was then performed at −70° C. for 1 to 3 days to intensify the signals of the filters. This probe detected an mRNA of about 9.5 kb, a transcript whose size agreed with that of the ORF identified from the nucleotide sequence, in almost all the tissues examined. Besides this band, a transcript of about 6.5 kb was predominantly expressed in the testis. Since this band remained unchanged even after the high stringent wash (0.1×SSC, at 65° C.), it was considered to be specifically expressed. The second transcript could-be an alternatively spliced product of BAZ2β, but no clone implying this event was found. It was also likely that expression of another gene closely related to BAZ2β was detected. In addition to these transcripts, several mRNAs were detected in most tissues. Such transcripts were considered to be derived from other genes each having an analogous sequence. Another analysis using another probe containing a bromodomain revealed the expression of the transcript of 6.5 kb only in the testis and of a 8.5 kb transcript in a wide range of tissues.

EXAMPLE 4 Isolation and Analysis of BAZ1β (BAZ1βS and BAZ1βL) Genes

[0105] (1) Identification of Novel Genes Containing a Bromodomain and Isolation of Their Full-Length Nucleotide Sequences

[0106] A BLAST search was performed against the EST database using the nucleotide sequence of the bromodomain motif from human GCN5 gene (Candau et al., (1996), Mol. Cell. Biol., 16:593-602). Several ESTs possibly coding a number of bromodomain genes were identified. Among them, an EST (Gnbank accession Number: AA01307) derived from a retinal cDNA library was found to be a novel gene.

[0107] Its full-length sequence was isolated. The full-length gene for EST AA01307 was cloned as follows. First, PCR primers nb3U (SEQ ID NO:31/TGGATGATGCTGAGGTGGATGA) and nb3L (SEQ ID NO:24/GGGGTGCTGGATGACATCATAG) were designed to obtain a product of 184 bp specific to the primers from a testis cDNA library. The amplified product was directly purified using a QIA Quick (Qiagen) purification column. The PCR product was used as a probe to screen the testis cDNA library (Clontech HL3024a), and the cDNA clone containing the EST sequence was used to re-screen the library. This process was repeated after joining the clones. As a result, two types of nucleotide sequences were obtained and designated BAZ1β. The two sequences were further designated BAZ1βS for the shorter sequence and BAZ1βL for the longer one. The shorter sequence consisted of 5,561 nucleotides and encoded a protein of 1527 amino acids; the longer sequence consisted of 5,573 nucleotides and encoded a protein of 1531 amino acids, containing a tandem repeat of TACAGACCCTCC in one frame. This repeat gave rise to an insertion of four amino acids LLQT at position 658, which interestingly resulted in an additional LXXLL motif. BAZ1βS had four LXXLL motifs initiated at positions 655, 658, 1000, and 1436, while BAZ1βL had five LXXLL motifs initiated at positions 655, 658, 663, 1004, and 1440. FIG. 13 shows an alignment of the portions having multiple LXXLL motifs of BAZ1βS and BAZ1βL.

[0108] To determine whether the variability of the LXXLL motif is attributed to alteration of splicing or polymorphism, a pair of primers consisting of NB3KK (SEQ ID NO:33/GAGTGCAGATAAGGGTGGCTTTTT) and NB3LL (SEQ ID NO:34/CCAATTCACCATAGTCTTCGGCTA), which correspond to both sides of the variable region, was prepared and used to amplify genomic DNA and cDNA. As a result, these primers amplified a product of the same size from both of the templates. This implies the sequence variant is generated within an intron. Therefore, the variation of the sequence is probably caused by polymorphism. This may affect the interaction with the nuclear receptors. The nucleotide sequence of BAZ1βS cDNA thus obtained is shown in SEQ ID NO:28, and the deduced amino acid sequence of the protein encoded by the cDNA is shown in SEQ ID NO:27. The nucleotide sequence of BAZ1βL cDNA is also shown in SEQ ID NO:30, and the deduced amino acid sequence of the protein encoded by the cDNA is shown in SEQ ID NO:29. All the nucleotide sequences were determined with automated sequencing apparatus ABI 377, using ABI dye terminator chemistry. Hybridization for the filter screening of the library was performed in ExpressHyb hybridization solution (Clontech) at 65° C. for 1 hour. The filters were washed at 65° C. until the final stringency reached 0.5×SSC and 0.1% SDS. Subsequently, the filters were autoradiographed at −70° C. for 4 days to intensify the signals or autoradiographed for 4 hours with the Fuji BAS system.

[0109] (2) Homology and Characteristics of the Motifs of the Transcriptional Regulator

[0110] The motifs of the proteins encoded by BAZ1βS and BAZ1βL genes were searched in PROSITE. The proteins were compared using a MAP program of a BCM search launcher (http://dot.imgen.bcm.tmc.edu:9331/multi-align/multi-align.html) under the default setting conditions; the output results were edited using a box shade program (http://ulrec3.unil.ch/software/BOX_form.htmlat). A nuclear transport signal was identified through PSORT (http://psort.nibb.ac.jp/form.html).

[0111] Several motifs characteristic of transcriptional regulators were found in both BAZ1βS and BAZ1βL. They were bromodomain, C4HC3 zinc finger (C4HC3ZF), and LXXLL motifs. LLXXLL motifs were present in the leucine-rich domain conserved among other BAZ family member protein genes and U13646 (FIG. 9). Although the importance of this domain has not been clarified, it can form a leucine zipper responsible for forming a dimer of the protein. It has been reported that such motifs are commonly found in the transcriptional regulators of eukaryotes (Busch and Sassone-Corsi, 1990) and that LXXLL motifs also interact with the nuclear receptors (Torchia et al., (1997), Nature, 387:677-684; Heery et al., (1997), Nature 387:733-736). That the predicted amino acid sequences have extensive similarity to several kinds of transcription regulators indicates the possibility that their genes function as transcriptional regulators. This is further supported by the fact that 13 nuclear localized consensus sequences (Robbins et al., (1991), Cell, 64:615-23) were found in total based on the prediction of the cellular localization of the proteins using the PSORT program. The predicted amino acid sequences exhibited the highest similarity to BAZ1α. They also showed similarity to the proteins encoded by BAZ2α, BAZ2β, and C. elegans bromodomain gene U13646. Among the six domains, the first domain existed in BAZ2α, BAZ2β, and U13646, but not in BAZ1βS, BAZ1βL, or BAZ1α. Comparing the whole structures of these gene products, the region between domains II and III is the most similar to that of BAZ1α (FIGS. 14-18). Like other members of BAZ family, these gene products also have motifs that are present in the protein assumed to be encoded by nematode (C. elegans) bromodomain gene U13646 (Wilson et al., (1994) Nature, 368:32-38) that is identified by analyzing genome sequences of the genes. Alignment of the sequences of BAZ1βS, other members of the BAZ family, and U13646 reveals that the most highly conserved regions are located between the center and the C terminus of the sequences (FIGS. 14-18). For U13646, this region is not depicted in the figures, and only N terminal region is aligned with that of BAZ1βS and BAZ1α.

[0112] (3) Chromosomal Mapping of BAZ1β

[0113] To create a chromosome map of BAZ1β, primers nb3S (SEQ ID NO:35/GAAACGGGAGGAGCTGAAAAAG) and nb3T (SEQ ID NO:36/CCTTCAGGGGTATCCACCAATC) were prepared and used to amplify the DNA obtained from each of the 24 human/rodent monochromosomal somatic cell lines (Dubois, B. L. and Naylor, S. (1993), Genomics, 16:315-319). The expected PCR product of 156 bp was amplified from GM10791 from two distinct cell lines, suggesting that the BAZ1β gene is likely to be located on human chromosome 7 (FIG. 19A). The locus of BAZ1β was determined using 91 radiation hybrid panels of GeneBridge 4 (Walter, M. A. et al., (1994), Nature Genetics, 7:22-28). The hybrid panels were screened by performing PCR with primers nb3S and nb3T again. The locus of this gene was identified by comparing the binary codes generated by assessing each hybrid as positive or negative for the amplification with the analogous codes for the markers constituting a framework map using the server located at http://www-genome.wi.mit.edu/cgi-bin/contig/rhmapper.pl. As a result, BAZ1β was confirmed to be mapped on chromosome 7q11-22 and also located between the markers D7S489 and D7S669 (FIG. 19B).

[0114] (4) Analysis of the BAZ1β Expression

[0115] The cDNA probe of 156 bp prepared by PCR for the testis cDNA using primers nb3S and nb3T was used for Northern analysis of 16 panels of normal tissues (FIG. 20). The probe was labeled with [α-³²P]dCTP by random priming and purified with a Chromaspin 10 column (Clontech). Hybridization for Northern analysis was performed at 65° C. for 1 hour in ExpressHyb hybridization solution (Clontech). The filters were washed at 65° C. until the final stringency reached 0.5×SSC and 0.1% SDS. Subsequently, autoradiography was performed at −70° C. for 4 days to intensify the signals of the filters or for 4 hours with a Fuji BAS system. This probe detected an mRNA of 7.5 kb in almost all the tissues examined. The transcript was analogous to a 7.0 kb transcript of BAZ1α.

EXAMPLE 5 Expression and Purification of BAZ2β Fusion Protein

[0116] Three constructs for BAZ2β were prepared with pGEX vector (Pharmacia) used to express fusion proteins in bacteria. Each of the three constructs contained the sequence corresponding to the amino acid positions 1-190, 1241-1584, or 1500-1970 of BAZ2α (FIG. 21). The expression of the fusion protein was mediated by the IPTG-inducible promoter located upstream from the cloning site. The expressed proteins were purified through an affinity matrix containing glutathione-Sepharose beads since the expressed protein was fused to glutathione-S-transferase (GST). Specifically, the GST fusion proteins were expressed and purified according to the instructions appended to GST purification modules (Pharmacia). The cultured volume was 400 ml, and proteins were induced by 0.1 mM IPTG at 30° C. overnight. Western blotting was performed using BioRad reagents included in an Alkaline Phosphatase Conjugate Substrate kit, according to the manual appended to the kit.

[0117] The results of analyzing the expressed protein on the 4-20% gradient SDS-polyacrylamide gel showed that the induced proteins were not detected in the bacterial cell lysates before purification (FIG. 22, Lanes 1, 4, and 5), indicating that the induction through the promoter was not strong in any construct. In any case, however, distinctive proteins (Table 2) with molecular weights corresponding to those predicted were detected (FIG. 23, Lanes 3, 8, and 9). To prove that the purified proteins were the desired fusion proteins, western blot was carried out using the anti-GST antibody. As a result, purified protein with the corresponding size predicted for each protein was detected. TABLE 2 Amino acid Predicted Detected Construct region MWT kDal MWT kDal BAZ2β.1  1-190 51 50 BAZ2β.9 1241-1584 67 65 BAZ2β.11 1500-1970 84 85

INDUSTRIAL APPLICABILITY

[0118] The present invention provides a novel transcriptional regulator having a bromodomain, DNA coding said transcriptional regulator, a vector containing said DNA, a transformant expressively retaining said DNA, an antibody binding to said transcriptional regulator, and the method of screening a compound binding to said transcriptional regulator. A transcriptional regulator and DNA of the present invention are expected to be used as indices to diagnose and treat cancer and proliferative diseases, and to screen a drug with a new action mechanism. A compound binding to a transcriptional regulator of the present invention could also be used as a pharmaceutical to treat the diseases described above.

1 73 1 1674 PRT Homo sapiens 1 Met Glu Asp Ala Ser Glu Ser Ser Arg Gly Val Ala Pro Leu Ile Asn 1 5 10 15 Asn Val Val Leu Pro Gly Ser Pro Leu Ser Leu Pro Val Ser Val Thr 20 25 30 Gly Cys Lys Ser His Arg Val Ala Asn Lys Lys Val Glu Ala Arg Ser 35 40 45 Glu Lys Leu Leu Pro Thr Ala Leu Pro Pro Ser Glu Pro Lys Val Asp 50 55 60 Gln Lys Leu Pro Arg Ser Ser Glu Arg Arg Gly Ser Gly Gly Gly Thr 65 70 75 80 Gln Phe Pro Ala Arg Ser Arg Ala Val Ala Ala Gly Glu Ala Ala Ala 85 90 95 Arg Gly Ala Ala Gly Pro Glu Arg Gly Ser Pro Leu Gly Arg Arg Val 100 105 110 Ser Pro Arg Cys Leu Cys Ser Gly Glu Gly Gly Gln Val Ala Val Gly 115 120 125 Val Ile Ala Gly Lys Arg Gly Arg Arg Gly Arg Asp Gly Ser Arg Arg 130 135 140 Ala Pro Gly Gly Arg Glu Met Pro Leu Leu His Arg Lys Pro Phe Val 145 150 155 160 Arg Gln Lys Pro Pro Ala Asp Leu Arg Pro Asp Glu Glu Val Phe Tyr 165 170 175 Cys Lys Val Thr Asn Glu Ile Phe Arg His Tyr Asp Asp Phe Phe Glu 180 185 190 Arg Thr Ile Leu Cys Asn Ser Leu Val Trp Ser Cys Ala Val Thr Gly 195 200 205 Arg Pro Gly Leu Thr Tyr Gln Glu Ala Leu Glu Ser Glu Lys Lys Ala 210 215 220 Arg Gln Asn Leu Gln Ser Phe Pro Glu Pro Leu Ile Ile Pro Val Leu 225 230 235 240 Tyr Leu Thr Ser Leu Thr His Arg Ser Arg Leu His Glu Ile Cys Asp 245 250 255 Asp Ile Phe Ala Tyr Val Lys Asp Arg Tyr Phe Val Glu Glu Thr Val 260 265 270 Glu Val Ile Arg Asn Asn Gly Ala Arg Leu Gln Cys Thr Ile Leu Glu 275 280 285 Val Leu Pro Pro Ser His Gln Asn Gly Phe Ala Asn Gly His Val Asn 290 295 300 Ser Val Asp Gly Glu Thr Ile Ile Ile Ser Asp Ser Asp Asp Ser Glu 305 310 315 320 Thr Gln Ser Cys Ser Phe Gln Asn Gly Lys Lys Lys Asp Ala Ile Asp 325 330 335 Pro Leu Leu Phe Lys Tyr Lys Val Gln Pro Thr Lys Lys Glu Leu His 340 345 350 Glu Ser Ala Ile Val Lys Ala Thr Gln Ile Ser Arg Arg Lys His Leu 355 360 365 Phe Ser Arg Asp Lys Leu Lys Leu Phe Leu Lys Gln His Cys Glu Pro 370 375 380 Gln Glu Gly Val Ile Lys Ile Lys Ala Ser Ser Leu Ser Thr Tyr Lys 385 390 395 400 Ile Ala Glu Gln Asp Phe Ser Tyr Phe Phe Pro Asp Asp Pro Pro Thr 405 410 415 Phe Ile Phe Ser Pro Ala Asn Arg Arg Arg Gly Arg Pro Pro Lys Arg 420 425 430 Ile His Ile Ser Gln Glu Asp Asn Val Ala Asn Lys Gln Thr Leu Ala 435 440 445 Ser Tyr Arg Ser Lys Ala Thr Lys Glu Arg Asp Lys Leu Leu Lys Gln 450 455 460 Glu Glu Met Lys Ser Leu Ala Phe Glu Lys Ala Lys Leu Lys Arg Glu 465 470 475 480 Lys Ala Asp Ala Leu Glu Ala Lys Lys Lys Glu Lys Glu Asp Lys Glu 485 490 495 Lys Lys Arg Glu Glu Leu Lys Lys Ile Val Glu Glu Glu Arg Leu Lys 500 505 510 Lys Lys Glu Glu Lys Glu Arg Leu Lys Val Glu Arg Glu Lys Glu Arg 515 520 525 Glu Lys Leu Arg Glu Glu Lys Arg Lys Tyr Val Glu Tyr Leu Lys Gln 530 535 540 Trp Ser Lys Pro Arg Glu Asp Met Glu Cys Asp Asp Leu Lys Glu Leu 545 550 555 560 Pro Glu Pro Thr Pro Val Lys Thr Arg Leu Pro Pro Glu Ile Phe Gly 565 570 575 Asp Ala Leu Met Val Leu Glu Phe Leu Asn Ala Phe Gly Glu Leu Phe 580 585 590 Asp Leu Gln Asp Glu Phe Pro Asp Gly Val Thr Leu Glu Val Leu Glu 595 600 605 Glu Ala Leu Val Gly Asn Asp Ser Glu Gly Pro Leu Cys Glu Leu Leu 610 615 620 Phe Phe Phe Leu Thr Ala Ile Phe Gln Ala Ile Ala Glu Glu Glu Glu 625 630 635 640 Glu Val Ala Lys Glu Gln Leu Thr Asp Ala Asp Thr Lys Gly Cys Ser 645 650 655 Leu Lys Ser Leu Asp Leu Asp Ser Cys Thr Leu Ser Glu Ile Leu Arg 660 665 670 Leu His Ile Leu Ala Ser Gly Ala Asp Val Thr Ser Ala Asn Ala Lys 675 680 685 Tyr Arg Tyr Gln Lys Arg Gly Gly Phe Asp Ala Thr Asp Asp Ala Cys 690 695 700 Met Glu Leu Arg Leu Ser Asn Pro Ser Leu Val Lys Lys Leu Ser Ser 705 710 715 720 Thr Ser Val Tyr Asp Leu Thr Pro Gly Glu Lys Met Lys Ile Leu His 725 730 735 Ala Leu Cys Gly Lys Leu Leu Thr Leu Val Ser Thr Arg Asp Phe Ile 740 745 750 Glu Asp Tyr Val Asp Ile Leu Arg Gln Ala Lys Gln Glu Phe Arg Glu 755 760 765 Leu Lys Ala Glu Gln His Arg Lys Glu Arg Glu Glu Ala Ala Ala Arg 770 775 780 Ile Arg Lys Arg Lys Glu Glu Lys Leu Lys Glu Gln Glu Gln Lys Met 785 790 795 800 Lys Glu Lys Gln Glu Lys Leu Lys Glu Asp Glu Gln Arg Asn Ser Thr 805 810 815 Ala Asp Ile Ser Ile Gly Glu Glu Glu Arg Glu Asp Phe Asp Thr Ser 820 825 830 Ile Glu Ser Lys Asp Thr Glu Gln Lys Glu Leu Asp Gln Asp Met Phe 835 840 845 Thr Glu Asp Glu Asp Asp Pro Gly Ser His Lys Arg Gly Arg Arg Gly 850 855 860 Lys Arg Gly Gln Asn Gly Phe Lys Glu Phe Thr Arg Gln Glu Gln Ile 865 870 875 880 Asn Cys Val Thr Arg Glu Leu Leu Thr Ala Asp Glu Glu Glu Ala Leu 885 890 895 Lys Gln Glu His Gln Arg Lys Glu Lys Glu Leu Leu Glu Lys Ile Gln 900 905 910 Ser Ala Ile Ala Cys Thr Asn Ile Phe Pro Leu Gly Arg Asp Arg Met 915 920 925 Tyr Arg Arg Tyr Trp Ile Phe Pro Ser Ile Pro Gly Leu Phe Ile Glu 930 935 940 Glu Asp Tyr Ser Gly Leu Thr Glu Asp Met Leu Leu Pro Arg Pro Ser 945 950 955 960 Ser Phe Gln Asn Asn Val Gln Ser Gln Asp Pro Gln Val Ser Thr Lys 965 970 975 Thr Gly Glu Pro Leu Met Ser Glu Ser Thr Ser Asn Ile Asp Gln Gly 980 985 990 Pro Arg Asp His Ser Val Gln Leu Pro Lys Pro Val His Lys Pro Asn 995 1000 1005 Arg Trp Cys Phe Tyr Ser Ser Cys Glu Gln Leu Asp Gln Leu Ile Glu 1010 1015 1020 Ala Leu Asn Ser Arg Gly His Arg Glu Ser Ala Leu Lys Glu Thr Leu 1025 1030 1035 1040 Leu Gln Glu Lys Ser Arg Ile Cys Ala Gln Leu Ala Arg Phe Ser Glu 1045 1050 1055 Glu Lys Phe His Phe Ser Asp Lys Pro Gln Pro Asp Ser Lys Pro Thr 1060 1065 1070 Tyr Ser Arg Gly Arg Ser Ser Asn Ala Tyr Asp Pro Ser Gln Met Cys 1075 1080 1085 Ala Glu Lys Gln Leu Glu Leu Arg Leu Arg Asp Phe Leu Leu Asp Ile 1090 1095 1100 Glu Asp Arg Ile Tyr Gln Gly Thr Leu Gly Ala Ile Lys Val Thr Asp 1105 1110 1115 1120 Arg His Ile Trp Arg Ser Ala Leu Glu Ser Gly Arg Tyr Glu Leu Leu 1125 1130 1135 Ser Glu Glu Asn Lys Glu Asn Gly Ile Ile Lys Thr Val Asn Glu Asp 1140 1145 1150 Val Glu Glu Met Glu Ile Asp Glu Gln Thr Lys Val Ile Val Lys Asp 1155 1160 1165 Arg Leu Leu Gly Ile Lys Thr Glu Thr Pro Ser Thr Val Ser Thr Asn 1170 1175 1180 Ala Ser Thr Pro Gln Ser Val Ser Ser Val Val His Tyr Leu Ala Met 1185 1190 1195 1200 Ala Leu Phe Gln Ile Glu Gln Gly Ile Glu Arg Arg Phe Leu Lys Ala 1205 1210 1215 Pro Leu Asp Ala Ser Asp Ser Gly Arg Ser Tyr Lys Thr Val Leu Asp 1220 1225 1230 Arg Trp Arg Glu Ser Leu Leu Ser Ser Ala Ser Leu Ser Gln Val Phe 1235 1240 1245 Leu His Leu Ser Thr Leu Asp Arg Ser Val Ile Trp Ser Lys Ser Ile 1250 1255 1260 Leu Asn Ala Arg Cys Lys Ile Cys Arg Lys Lys Gly Asp Ala Glu Asn 1265 1270 1275 1280 Met Val Leu Cys Asp Gly Cys Asp Arg Gly His His Thr Tyr Cys Val 1285 1290 1295 Arg Pro Lys Leu Lys Thr Val Pro Glu Gly Asp Trp Phe Cys Pro Glu 1300 1305 1310 Cys Arg Pro Lys Gln Arg Cys Arg Arg Leu Ser Phe Arg Gln Arg Pro 1315 1320 1325 Ser Leu Glu Ser Asp Glu Asp Val Glu Asp Ser Met Gly Gly Glu Asp 1330 1335 1340 Asp Glu Val Asp Gly Asp Glu Glu Glu Gly Gln Ser Glu Glu Glu Glu 1345 1350 1355 1360 Tyr Glu Val Glu Gln Asp Glu Asp Asp Ser Gln Glu Glu Glu Glu Val 1365 1370 1375 Ser Leu Pro Lys Arg Gly Arg Pro Gln Val Arg Leu Pro Val Lys Thr 1380 1385 1390 Arg Gly Lys Leu Ser Ser Ser Phe Ser Ser Arg Gly Gln Gln Gln Glu 1395 1400 1405 Pro Gly Arg Tyr Pro Ser Arg Ser Gln Gln Ser Thr Pro Lys Thr Thr 1410 1415 1420 Val Ser Ser Lys Thr Gly Arg Ser Leu Arg Lys Ile Asn Ser Ala Pro 1425 1430 1435 1440 Pro Thr Glu Thr Lys Ser Leu Arg Ile Ala Ser Arg Ser Thr Arg His 1445 1450 1455 Ser His Gly Pro Leu Gln Ala Asp Val Phe Val Glu Leu Leu Ser Pro 1460 1465 1470 Arg Arg Lys Arg Arg Gly Arg Lys Ser Ala Asn Asn Thr Pro Glu Asn 1475 1480 1485 Ser Pro Asn Phe Pro Asn Phe Arg Val Ile Ala Thr Lys Ser Ser Glu 1490 1495 1500 Gln Ser Arg Ser Val Asn Ile Ala Ser Lys Leu Ser Leu Gln Glu Ser 1505 1510 1515 1520 Glu Ser Lys Arg Arg Cys Arg Lys Arg Gln Ser Pro Glu Pro Ser Pro 1525 1530 1535 Val Thr Leu Gly Arg Arg Ser Ser Gly Arg Gln Gly Gly Val His Glu 1540 1545 1550 Leu Ser Ala Phe Glu Gln Leu Val Val Glu Leu Val Arg His Asp Asp 1555 1560 1565 Ser Trp Pro Phe Leu Lys Leu Val Ser Lys Ile Gln Val Pro Asp Tyr 1570 1575 1580 Tyr Asp Ile Ile Lys Lys Pro Ile Ala Leu Asn Ile Ile Arg Glu Lys 1585 1590 1595 1600 Val Asn Lys Cys Glu Tyr Lys Leu Ala Ser Glu Phe Ile Asp Asp Ile 1605 1610 1615 Glu Leu Met Phe Ser Asn Cys Phe Glu Tyr Asn Pro Arg Asn Thr Ser 1620 1625 1630 Glu Ala Lys Ala Gly Thr Arg Leu Gln Ala Phe Phe His Ile Gln Ala 1635 1640 1645 Gln Lys Leu Gly Leu His Val Thr Pro Ser Asn Val Asp Gln Val Ser 1650 1655 1660 Thr Pro Pro Ala Ala Lys Lys Ser Arg Ile 1665 1670 2 5934 DNA Homo sapiens CDS (125)...(5146) misc_feature (1)...(5934) n = A,T,C or G 2 gaattccggc ttttcccatc gtgtagtcaa gagtctgtgc cagacttgaa ggctttactt 60 tgttagccat gtgtttatga acccccagcg ctttccctag atcttttggc tgataatctc 120 aaac atg gag gat gct tct gaa tct tca cga ggg gtt gct cca tta att 169 Met Glu Asp Ala Ser Glu Ser Ser Arg Gly Val Ala Pro Leu Ile 1 5 10 15 aat aat gta gtt ctc cca ggc tct ccg ctg tct ctt cct gta tca gtg 217 Asn Asn Val Val Leu Pro Gly Ser Pro Leu Ser Leu Pro Val Ser Val 20 25 30 aca ggc tgt aaa agt cat cga gta gcc aat aaa aag gta gaa gcg agg 265 Thr Gly Cys Lys Ser His Arg Val Ala Asn Lys Lys Val Glu Ala Arg 35 40 45 agt gaa aag ctc ctc cca aca gct ctt cct cct tca gag ccg aaa gta 313 Ser Glu Lys Leu Leu Pro Thr Ala Leu Pro Pro Ser Glu Pro Lys Val 50 55 60 gat cag aaa ctt ccc agg agc tcc gag agg cgg gga agt ggc ggt ggg 361 Asp Gln Lys Leu Pro Arg Ser Ser Glu Arg Arg Gly Ser Gly Gly Gly 65 70 75 acg caa ttc ccc gcg cgg agt cgg gca gtg gca gcg gga gaa gcg gca 409 Thr Gln Phe Pro Ala Arg Ser Arg Ala Val Ala Ala Gly Glu Ala Ala 80 85 90 95 gcc agg ggc gcg gcg ggg ccg gag aga ggc agt ccc ctg gga aga cgg 457 Ala Arg Gly Ala Ala Gly Pro Glu Arg Gly Ser Pro Leu Gly Arg Arg 100 105 110 gtc tcc cct cgt tgc ctt tgt agt gga gaa ggt gga caa gtg gca gtc 505 Val Ser Pro Arg Cys Leu Cys Ser Gly Glu Gly Gly Gln Val Ala Val 115 120 125 ggc gtg atc gca ggg aag cgg ggc cgg cgc ggg cgc gac ggg tcc agg 553 Gly Val Ile Ala Gly Lys Arg Gly Arg Arg Gly Arg Asp Gly Ser Arg 130 135 140 cga gcc ccg ggc gga cgg gag atg ccg ctg cta cac cga aag ccg ttt 601 Arg Ala Pro Gly Gly Arg Glu Met Pro Leu Leu His Arg Lys Pro Phe 145 150 155 gtg aga cag aag ccg ccc gcg gac ctg cgg ccc gac gag gaa gtt ttc 649 Val Arg Gln Lys Pro Pro Ala Asp Leu Arg Pro Asp Glu Glu Val Phe 160 165 170 175 tac tgt aaa gtc acc aac gag atc ttc cgc cac tac gat gac ttt ttt 697 Tyr Cys Lys Val Thr Asn Glu Ile Phe Arg His Tyr Asp Asp Phe Phe 180 185 190 gaa cga acc att ctg tgc aac agc ctt gtg tgg agt tgt gct gtg acg 745 Glu Arg Thr Ile Leu Cys Asn Ser Leu Val Trp Ser Cys Ala Val Thr 195 200 205 ggt aga cct gga ctg acg tat cag gaa gca ctt gag tca gaa aaa aaa 793 Gly Arg Pro Gly Leu Thr Tyr Gln Glu Ala Leu Glu Ser Glu Lys Lys 210 215 220 gca aga cag aat ctt cag agt ttt cca gaa cca cta att att cca gtt 841 Ala Arg Gln Asn Leu Gln Ser Phe Pro Glu Pro Leu Ile Ile Pro Val 225 230 235 tta tac ttg acc agc ctt acc cat cgt tcg cgc tta cat gaa att tgt 889 Leu Tyr Leu Thr Ser Leu Thr His Arg Ser Arg Leu His Glu Ile Cys 240 245 250 255 gat gat atc ttt gca tat gtc aag gat cga tat ttt gtc gaa gaa act 937 Asp Asp Ile Phe Ala Tyr Val Lys Asp Arg Tyr Phe Val Glu Glu Thr 260 265 270 gtg gaa gtc att agg aac aat ggt gca agg ttg cag tgt acg att ttg 985 Val Glu Val Ile Arg Asn Asn Gly Ala Arg Leu Gln Cys Thr Ile Leu 275 280 285 gaa gtc ctc cct cca tca cat caa aat ggt ttt gct aat gga cat gtt 1033 Glu Val Leu Pro Pro Ser His Gln Asn Gly Phe Ala Asn Gly His Val 290 295 300 aac agt gtg gat gga gaa act att atc atc agt gat agt gat gat tca 1081 Asn Ser Val Asp Gly Glu Thr Ile Ile Ile Ser Asp Ser Asp Asp Ser 305 310 315 gaa aca caa agc tgt tct ttt caa aat ggg aag aaa aaa gat gca att 1129 Glu Thr Gln Ser Cys Ser Phe Gln Asn Gly Lys Lys Lys Asp Ala Ile 320 325 330 335 gat ccc tta cta ttc aag tat aaa gtg caa ccc act aaa aaa gaa tta 1177 Asp Pro Leu Leu Phe Lys Tyr Lys Val Gln Pro Thr Lys Lys Glu Leu 340 345 350 cat gag tct gct att gtt aaa gca aca caa atc agc cgg aga aaa cac 1225 His Glu Ser Ala Ile Val Lys Ala Thr Gln Ile Ser Arg Arg Lys His 355 360 365 cta ttt tct cgt gat aaa cta aag ctt ttt ctg aag caa cac tgt gaa 1273 Leu Phe Ser Arg Asp Lys Leu Lys Leu Phe Leu Lys Gln His Cys Glu 370 375 380 cca caa gaa gga gtc att aaa ata aag gca tca tct ctt tca acg tat 1321 Pro Gln Glu Gly Val Ile Lys Ile Lys Ala Ser Ser Leu Ser Thr Tyr 385 390 395 aaa ata gca gaa caa gat ttt tct tat ttc ttc cct gat gat cca ccc 1369 Lys Ile Ala Glu Gln Asp Phe Ser Tyr Phe Phe Pro Asp Asp Pro Pro 400 405 410 415 aca ttt atc ttc agt cct gct aac aga cga aga ggg aga cct ccc aaa 1417 Thr Phe Ile Phe Ser Pro Ala Asn Arg Arg Arg Gly Arg Pro Pro Lys 420 425 430 cga ata cat att agt caa gag gac aat gtt gct aat aaa cag act ctt 1465 Arg Ile His Ile Ser Gln Glu Asp Asn Val Ala Asn Lys Gln Thr Leu 435 440 445 gca agt tat agg agc aaa gct act aaa gaa aga gat aaa ctt ttg aaa 1513 Ala Ser Tyr Arg Ser Lys Ala Thr Lys Glu Arg Asp Lys Leu Leu Lys 450 455 460 caa gaa gaa atg aag tca ctg gct ttt gaa aag gct aaa tta aaa aga 1561 Gln Glu Glu Met Lys Ser Leu Ala Phe Glu Lys Ala Lys Leu Lys Arg 465 470 475 gaa aaa gca gat gcc cta gaa gcg aag aaa aaa gaa aaa gaa gat aaa 1609 Glu Lys Ala Asp Ala Leu Glu Ala Lys Lys Lys Glu Lys Glu Asp Lys 480 485 490 495 gag aaa aag agg gaa gaa ttg aaa aaa att gtt gaa gaa gag aga cta 1657 Glu Lys Lys Arg Glu Glu Leu Lys Lys Ile Val Glu Glu Glu Arg Leu 500 505 510 aag aaa aaa gaa gaa aaa gag agg ctt aaa gta gaa aga gaa aag gaa 1705 Lys Lys Lys Glu Glu Lys Glu Arg Leu Lys Val Glu Arg Glu Lys Glu 515 520 525 aga gag aag tta cgt gaa gaa aag cga aag tat gtg gaa tac tta aaa 1753 Arg Glu Lys Leu Arg Glu Glu Lys Arg Lys Tyr Val Glu Tyr Leu Lys 530 535 540 cag tgg agt aaa cct aga gaa gat atg gaa tgt gat gac ctt aag gaa 1801 Gln Trp Ser Lys Pro Arg Glu Asp Met Glu Cys Asp Asp Leu Lys Glu 545 550 555 ctt cca gaa cca aca cca gtg aaa act aga cta cct cct gaa atc ttt 1849 Leu Pro Glu Pro Thr Pro Val Lys Thr Arg Leu Pro Pro Glu Ile Phe 560 565 570 575 ggt gat gct ctg atg gtt ttg gag ttc ctt aat gca ttt ggg gaa ctt 1897 Gly Asp Ala Leu Met Val Leu Glu Phe Leu Asn Ala Phe Gly Glu Leu 580 585 590 ttt gat ctt caa gat gag ttt cct gat gga gta acc cta gaa gta tta 1945 Phe Asp Leu Gln Asp Glu Phe Pro Asp Gly Val Thr Leu Glu Val Leu 595 600 605 gag gaa gct ctt gtt gga aat gac agt gaa ggc cca ctg tgt gaa ttg 1993 Glu Glu Ala Leu Val Gly Asn Asp Ser Glu Gly Pro Leu Cys Glu Leu 610 615 620 ctt ttt ttc ttc ctg act gca atc ttc cag gca ata gct gaa gaa gaa 2041 Leu Phe Phe Phe Leu Thr Ala Ile Phe Gln Ala Ile Ala Glu Glu Glu 625 630 635 gag gaa gta gcc aaa gag caa cta act gat gct gac acc aaa ggc tgc 2089 Glu Glu Val Ala Lys Glu Gln Leu Thr Asp Ala Asp Thr Lys Gly Cys 640 645 650 655 agt ttg aaa agt ttg gat ctt gat agc tgc act ctt tca gaa atc ctc 2137 Ser Leu Lys Ser Leu Asp Leu Asp Ser Cys Thr Leu Ser Glu Ile Leu 660 665 670 aga ctg cac atc tta gct tca ggt gct gat gta aca tca gca aat gca 2185 Arg Leu His Ile Leu Ala Ser Gly Ala Asp Val Thr Ser Ala Asn Ala 675 680 685 aag tat aga tat caa aaa cga gga gga ttt gat gct aca gat gat gct 2233 Lys Tyr Arg Tyr Gln Lys Arg Gly Gly Phe Asp Ala Thr Asp Asp Ala 690 695 700 tgt atg gag ctt cgt ttg agc aat ccc agt cta gtg aag aaa ctg tca 2281 Cys Met Glu Leu Arg Leu Ser Asn Pro Ser Leu Val Lys Lys Leu Ser 705 710 715 agc acc tca gtg tat gat ttg aca cca gga gaa aaa atg aag ata ctc 2329 Ser Thr Ser Val Tyr Asp Leu Thr Pro Gly Glu Lys Met Lys Ile Leu 720 725 730 735 cat gct ctc tgt gga aag cta ctg acc cta gtt tca act agg gat ttt 2377 His Ala Leu Cys Gly Lys Leu Leu Thr Leu Val Ser Thr Arg Asp Phe 740 745 750 att gaa gat tat gtt gat ata tta cga cag gca aag cag gag ttc cgg 2425 Ile Glu Asp Tyr Val Asp Ile Leu Arg Gln Ala Lys Gln Glu Phe Arg 755 760 765 gaa tta aaa gca gaa caa cat cga aaa gag agg gaa gaa gca gct gcc 2473 Glu Leu Lys Ala Glu Gln His Arg Lys Glu Arg Glu Glu Ala Ala Ala 770 775 780 aga att cgt aaa agg aag gaa gaa aaa ctt aag gag caa gaa caa aaa 2521 Arg Ile Arg Lys Arg Lys Glu Glu Lys Leu Lys Glu Gln Glu Gln Lys 785 790 795 atg aaa gag aaa caa gaa aaa ctg aaa gaa gat gag caa aga aat tca 2569 Met Lys Glu Lys Gln Glu Lys Leu Lys Glu Asp Glu Gln Arg Asn Ser 800 805 810 815 acg gca gat ata tct att ggg gag gaa gaa agg gaa gat ttt gat act 2617 Thr Ala Asp Ile Ser Ile Gly Glu Glu Glu Arg Glu Asp Phe Asp Thr 820 825 830 agc att gag agc aaa gac aca gag caa aag gaa tta gat caa gat atg 2665 Ser Ile Glu Ser Lys Asp Thr Glu Gln Lys Glu Leu Asp Gln Asp Met 835 840 845 ttc act gaa gat gaa gat gac cca gga tca cat aaa aga ggc aga agg 2713 Phe Thr Glu Asp Glu Asp Asp Pro Gly Ser His Lys Arg Gly Arg Arg 850 855 860 ggg aaa aga gga caa aat gga ttt aaa gaa ttt aca agg caa gaa cag 2761 Gly Lys Arg Gly Gln Asn Gly Phe Lys Glu Phe Thr Arg Gln Glu Gln 865 870 875 atc aac tgt gta aca aga gag ctt ctt act gct gat gag gaa gaa gca 2809 Ile Asn Cys Val Thr Arg Glu Leu Leu Thr Ala Asp Glu Glu Glu Ala 880 885 890 895 tta aaa cag gaa cac caa cga aaa gag aaa gag ctc tta gaa aaa atc 2857 Leu Lys Gln Glu His Gln Arg Lys Glu Lys Glu Leu Leu Glu Lys Ile 900 905 910 caa agt gcc ata gcc tgt acc aat atc ttt ccc ttg ggt cgc gac cgc 2905 Gln Ser Ala Ile Ala Cys Thr Asn Ile Phe Pro Leu Gly Arg Asp Arg 915 920 925 atg tat aga cga tac tgg att ttc cct tct att cct gga ctc ttt att 2953 Met Tyr Arg Arg Tyr Trp Ile Phe Pro Ser Ile Pro Gly Leu Phe Ile 930 935 940 gaa gag gat tat tct ggt ctt act gaa gac atg ctg ttg cct aga cct 3001 Glu Glu Asp Tyr Ser Gly Leu Thr Glu Asp Met Leu Leu Pro Arg Pro 945 950 955 tca tca ttt cag aat aat gta cag tct caa gat cct cag gta tcc act 3049 Ser Ser Phe Gln Asn Asn Val Gln Ser Gln Asp Pro Gln Val Ser Thr 960 965 970 975 aaa act gga gag cct ttg atg tct gaa tct acc tcc aac att gac caa 3097 Lys Thr Gly Glu Pro Leu Met Ser Glu Ser Thr Ser Asn Ile Asp Gln 980 985 990 ggt cca cgt gac cat tct gtg cag ctg cca aaa cca gtg cat aag cca 3145 Gly Pro Arg Asp His Ser Val Gln Leu Pro Lys Pro Val His Lys Pro 995 1000 1005 aat cgg tgg tgc ttt tac agt tct tgt gaa cag cta gac cag ctt att 3193 Asn Arg Trp Cys Phe Tyr Ser Ser Cys Glu Gln Leu Asp Gln Leu Ile 1010 1015 1020 gaa gct ctt aat tct aga gga cat aga gaa agt gcc tta aaa gaa act 3241 Glu Ala Leu Asn Ser Arg Gly His Arg Glu Ser Ala Leu Lys Glu Thr 1025 1030 1035 ttg tta caa gag aaa agc aga ata tgt gca cag cta gcc cgt ttt tct 3289 Leu Leu Gln Glu Lys Ser Arg Ile Cys Ala Gln Leu Ala Arg Phe Ser 1040 1045 1050 1055 gaa gag aaa ttt cat ttt tca gac aaa cct cag cct gat agc aaa cca 3337 Glu Glu Lys Phe His Phe Ser Asp Lys Pro Gln Pro Asp Ser Lys Pro 1060 1065 1070 aca tat agt cgg gga aga tct tcc aat gca tat gat cca tct cag atg 3385 Thr Tyr Ser Arg Gly Arg Ser Ser Asn Ala Tyr Asp Pro Ser Gln Met 1075 1080 1085 tgt gca gaa aag caa ctt gaa cta agg ctg aga gat ttt ctt tta gat 3433 Cys Ala Glu Lys Gln Leu Glu Leu Arg Leu Arg Asp Phe Leu Leu Asp 1090 1095 1100 att gaa gat aga atc tac caa gga aca tta gga gcc atc aag gtt aca 3481 Ile Glu Asp Arg Ile Tyr Gln Gly Thr Leu Gly Ala Ile Lys Val Thr 1105 1110 1115 gat cga cat atc tgg aga tca gca tta gaa agt gga cgg tat gag ctg 3529 Asp Arg His Ile Trp Arg Ser Ala Leu Glu Ser Gly Arg Tyr Glu Leu 1120 1125 1130 1135 tta agt gag gaa aac aag gaa aat ggg ata att aaa act gtg aat gaa 3577 Leu Ser Glu Glu Asn Lys Glu Asn Gly Ile Ile Lys Thr Val Asn Glu 1140 1145 1150 gac gta gaa gag atg gaa att gat gaa caa aca aag gtc ata gta aaa 3625 Asp Val Glu Glu Met Glu Ile Asp Glu Gln Thr Lys Val Ile Val Lys 1155 1160 1165 gac aga ctt ttg ggg ata aaa aca gaa act cca agt act gta tca aca 3673 Asp Arg Leu Leu Gly Ile Lys Thr Glu Thr Pro Ser Thr Val Ser Thr 1170 1175 1180 aat gca agt aca cca caa tca gtg agc agt gtg gtt cat tat ctg gca 3721 Asn Ala Ser Thr Pro Gln Ser Val Ser Ser Val Val His Tyr Leu Ala 1185 1190 1195 atg gca ctc ttt caa ata gag cag ggc att gag cgg cgt ttt ctg aaa 3769 Met Ala Leu Phe Gln Ile Glu Gln Gly Ile Glu Arg Arg Phe Leu Lys 1200 1205 1210 1215 gct cca ctt gat gcc agt gac agt ggg cgt tct tat aaa aca gtt ctg 3817 Ala Pro Leu Asp Ala Ser Asp Ser Gly Arg Ser Tyr Lys Thr Val Leu 1220 1225 1230 gac cgt tgg aga gag tct ctc ctt tct tct gct agt cta tcc caa gtt 3865 Asp Arg Trp Arg Glu Ser Leu Leu Ser Ser Ala Ser Leu Ser Gln Val 1235 1240 1245 ttt ctt cac cta tcc acc ttg gat cgt agc gtg ata tgg tct aaa tct 3913 Phe Leu His Leu Ser Thr Leu Asp Arg Ser Val Ile Trp Ser Lys Ser 1250 1255 1260 ata ctg aat gcg cgt tgc aag ata tgt cga aag aaa ggc gat gct gaa 3961 Ile Leu Asn Ala Arg Cys Lys Ile Cys Arg Lys Lys Gly Asp Ala Glu 1265 1270 1275 aac atg gtt ctt tgt gat ggc tgt gat agg ggt cat cat acc tac tgt 4009 Asn Met Val Leu Cys Asp Gly Cys Asp Arg Gly His His Thr Tyr Cys 1280 1285 1290 1295 gtt cga cca aag ctc aag act gtg cct gaa gga gac tgg ttt tgt cca 4057 Val Arg Pro Lys Leu Lys Thr Val Pro Glu Gly Asp Trp Phe Cys Pro 1300 1305 1310 gaa tgt cga cca aag caa cgt tgt aga aga ctg tcc ttt aga cag aga 4105 Glu Cys Arg Pro Lys Gln Arg Cys Arg Arg Leu Ser Phe Arg Gln Arg 1315 1320 1325 cca tcc ttg gaa agt gat gaa gat gtg gaa gac agt atg gga ggt gag 4153 Pro Ser Leu Glu Ser Asp Glu Asp Val Glu Asp Ser Met Gly Gly Glu 1330 1335 1340 gat gat gaa gtt gat ggc gat gaa gaa gaa ggt caa agt gag gag gaa 4201 Asp Asp Glu Val Asp Gly Asp Glu Glu Glu Gly Gln Ser Glu Glu Glu 1345 1350 1355 gag tat gag gta gaa caa gat gaa gat gac tct caa gaa gag gaa gaa 4249 Glu Tyr Glu Val Glu Gln Asp Glu Asp Asp Ser Gln Glu Glu Glu Glu 1360 1365 1370 1375 gtc agc cta ccc aaa cga gga aga cca caa gtt aga ttg cca gtt aaa 4297 Val Ser Leu Pro Lys Arg Gly Arg Pro Gln Val Arg Leu Pro Val Lys 1380 1385 1390 aca aga ggg aaa ctt agc tct tct ttc tca agt cgt ggc caa caa caa 4345 Thr Arg Gly Lys Leu Ser Ser Ser Phe Ser Ser Arg Gly Gln Gln Gln 1395 1400 1405 gaa cct gga aga tac cct tcc agg agt cag cag agc aca ccc aaa aca 4393 Glu Pro Gly Arg Tyr Pro Ser Arg Ser Gln Gln Ser Thr Pro Lys Thr 1410 1415 1420 act gtt tct tct aaa act ggt aga agc cta aga aag ata aac tct gct 4441 Thr Val Ser Ser Lys Thr Gly Arg Ser Leu Arg Lys Ile Asn Ser Ala 1425 1430 1435 cct cct aca gaa aca aaa tct tta aga att gcc agt cgt tct act cgc 4489 Pro Pro Thr Glu Thr Lys Ser Leu Arg Ile Ala Ser Arg Ser Thr Arg 1440 1445 1450 1455 cac agt cat ggc cca ctg caa gca gat gta ttt gtg gaa ttg ctt agt 4537 His Ser His Gly Pro Leu Gln Ala Asp Val Phe Val Glu Leu Leu Ser 1460 1465 1470 cct cgt aga aaa cgc aga ggc agg aaa agt gct aat aat aca cca gaa 4585 Pro Arg Arg Lys Arg Arg Gly Arg Lys Ser Ala Asn Asn Thr Pro Glu 1475 1480 1485 aat agt ccc aac ttc cct aac ttc aga gtc att gcc aca aag tca agt 4633 Asn Ser Pro Asn Phe Pro Asn Phe Arg Val Ile Ala Thr Lys Ser Ser 1490 1495 1500 gaa cag tca aga tct gta aat att gct tca aaa ctt tct ctc caa gag 4681 Glu Gln Ser Arg Ser Val Asn Ile Ala Ser Lys Leu Ser Leu Gln Glu 1505 1510 1515 agt gaa tcc aaa aga aga tgc aga aaa aga caa tct cca gag cca tcg 4729 Ser Glu Ser Lys Arg Arg Cys Arg Lys Arg Gln Ser Pro Glu Pro Ser 1520 1525 1530 1535 cct gtg aca ctg ggt cga agg agt tct ggc cga cag gga gga gtt cat 4777 Pro Val Thr Leu Gly Arg Arg Ser Ser Gly Arg Gln Gly Gly Val His 1540 1545 1550 gaa ttg tct gct ttt gaa caa ctt gtt gta gaa ttg gta cga cat gat 4825 Glu Leu Ser Ala Phe Glu Gln Leu Val Val Glu Leu Val Arg His Asp 1555 1560 1565 gac agc tgg cct ttt ttg aaa ctt gtt tct aaa atc cag gtc cca gac 4873 Asp Ser Trp Pro Phe Leu Lys Leu Val Ser Lys Ile Gln Val Pro Asp 1570 1575 1580 tac tat gac atc atc aaa aag ccc att gcc tta aat ata att cgt gaa 4921 Tyr Tyr Asp Ile Ile Lys Lys Pro Ile Ala Leu Asn Ile Ile Arg Glu 1585 1590 1595 aaa gtg aat aag tgt gaa tat aaa tta gca tct gag ttt att gat gac 4969 Lys Val Asn Lys Cys Glu Tyr Lys Leu Ala Ser Glu Phe Ile Asp Asp 1600 1605 1610 1615 att gag tta atg ttt tcg aac tgc ttt gaa tac aac cct cgt aac aca 5017 Ile Glu Leu Met Phe Ser Asn Cys Phe Glu Tyr Asn Pro Arg Asn Thr 1620 1625 1630 agt gaa gca aaa gct gga act agg ctt caa gca ttt ttt cat att cag 5065 Ser Glu Ala Lys Ala Gly Thr Arg Leu Gln Ala Phe Phe His Ile Gln 1635 1640 1645 gct caa aag ctt gga ctc cac gtc aca ccc agt aat gtg gac caa gtt 5113 Ala Gln Lys Leu Gly Leu His Val Thr Pro Ser Asn Val Asp Gln Val 1650 1655 1660 agc aca cca ccg gct gcg aaa aag tca cga atc tgactttgtc cttctaaagg 5166 Ser Thr Pro Pro Ala Ala Lys Lys Ser Arg Ile 1665 1670 atatatttga agaaaaacaa attgttcatg aaaatggaac attaaatcat gctgtataaa 5226 gcaataacaa acaattgatt gaccacatga aagtgtggcc tgcactatat tctcaatttt 5286 aatattaagc actcaggaga atgtaggaaa gatatccttt gctacagttt tgttcagtat 5346 ctaataagtt tgatagatgt attggataca gtactggttt acagaggttt ttgtacattt 5406 ttganatcat tcatgtgtcc agagatcttg gaaaatattt tttcacccac gatttatttt 5466 gttattgatg atttattttt aaagtggtgg tattaaggga gagttatcta catggatgag 5526 tcttccgcta tagcacagtt tagaaaaggt gtttatgtct taattaattg tttgagtaca 5586 ttctttcaac actacacatg aatgaatcca atcttataac cttgaagtgc tgtaccagtg 5646 ctggctgcag gtattaagtc caagtttatt aactagatat ttatttagta ttgagagtaa 5706 tttgtgaatt tgttttgtat ttataaaatt tatacctgga aaatgttcct taatgtttta 5766 aaccttttac tgtgttttta ttcctctaac ttccttaatg atcaatcaaa aaaagtaaca 5826 ccctcccttt ttcctgacag ttctttcagc tttacagaac tgtattataa gttcgatgta 5886 taattttaac tgttcaaata aaatacattt ttccaataaa aaaaaaaa 5934 3 140 DNA Homo sapiens 3 gactaccacg acatcatcaa gaaaccaatg gatctgggca cagtcaagcg gaaaatggac 60 aatcgcgagt acaagagcgc gccggaattt gccgccgacg tgcgattaat attcaccaac 120 tgctacaagt acaatccgcc 140 4 23 DNA Artificial Sequence Synthetically generated primer 4 agaaaaagac aatctccaga gca 23 5 24 DNA Artificial Sequence Synthetically generated primer 5 gctgtcatca tgtcgtacca attc 24 6 24 DNA Artificial Sequence Synthetically generated primer 6 aacacaagtg aagcaaaagc tgga 24 7 24 DNA Artificial Sequence Synthetically generated primer 7 gtggtgtgct aacttggtcc acat 24 8 25 DNA Artificial Sequence Synthetically generated primer 8 cccatcgtga gtcaagagtg tctgt 25 9 24 DNA Artificial Sequence Synthetically generated primer 9 ctcgcttcta cctttttatt ggct 24 10 25 DNA Artificial Sequence Synthetically generated primer 10 tcatcatctc tgccccctct gtctg 25 11 24 DNA Artificial Sequence Synthetically generated primer 11 gacgcctgct tcaccacctt cttg 24 12 24 DNA Artificial Sequence Synthetically generated primer 12 tcatgtggtc aatcaattgt ttgt 24 13 1878 PRT Homo sapiens VARIANT (1)...(1878) Xaa = Any Amino Acid 13 Met Glu Met Glu Ala Asn Glu Ala Asn Asp His Phe Asn Phe Thr Gly 1 5 10 15 Leu Pro Pro Ala Pro Ala Ala Ser Gly Leu Lys Pro Ser Pro Ser Ser 20 25 30 Gly Glu Gly Leu Tyr Thr Asn Gly Ser Pro Met Asn Phe Pro Gln Gln 35 40 45 Gly Lys Ser Leu Asn Gly Asp Val Asn Val Asn Gly Leu Ser Thr Val 50 55 60 Ser His Thr Thr Thr Ser Gly Ile Leu Asn Ser Ala Pro His Ser Ser 65 70 75 80 Ser Thr Ser His Leu His His Pro Ser Val Ala Tyr Asp Cys Leu Trp 85 90 95 Asn Tyr Ser Gln Tyr Pro Ser Ala Asn Pro Gly Ser Asn Leu Lys Asp 100 105 110 Pro Pro Leu Leu Ser Gln Phe Ser Gly Gly Gln Tyr Pro Leu Asn Gly 115 120 125 Ile Leu Gly Gly Ser Arg Gln Pro Ser Ser Pro Ser His Asn Thr Asn 130 135 140 Leu Arg Ala Gly Ser Gln Lys Phe Trp Ala Asn Gly Thr His Ser Pro 145 150 155 160 Met Gly Leu Asn Phe Asp Ser Gln Glu Leu Tyr Asp Ser Phe Pro Asp 165 170 175 Gln Asn Phe Glu Glu Val Cys Ser Gly Ile His Pro Asp Glu Ala Ala 180 185 190 Glu Lys Glu Met Thr Ser Val Val Ala Glu Asn Gly Thr Gly Leu Val 195 200 205 Cys Ser Leu Glu Leu Glu Glu Xaa Gln Pro Glu Leu Lys Met Cys Gly 210 215 220 Tyr Asn Gly Ser Val Pro Ser Val Glu Ser Leu His Gln Glu Val Ser 225 230 235 240 Val Leu Val Pro Asp Pro Thr Val Ser Cys Leu Asp Asp Pro Ser His 245 250 255 Leu Pro Asp Gln Leu Glu Asp Thr Pro Ile Leu Ser Glu Asp Ser Leu 260 265 270 Glu Pro Phe Asn Ser Leu Ala Pro Glu Pro Val Ser Gly Gly Leu Tyr 275 280 285 Gly Ile Asp Asp Thr Glu Leu Met Gly Ala Glu Asp Lys Leu Pro Leu 290 295 300 Xaa Asp Ser Pro Val Ile Ser Ala Leu Asp Cys Pro Ser Leu Asn Asn 305 310 315 320 Ala Thr Ala Phe Ser Leu Leu Ala Asp Asp Ser Gln Thr Ser Thr Ser 325 330 335 Ile Phe Ala Ser Pro Thr Ser Pro Pro Val Leu Gly Glu Ser Val Leu 340 345 350 Gln Asp Asn Ser Phe Asp Leu Asn Asn Gly Ser Asp Ala Glu Gln Glu 355 360 365 Glu Met Glu Thr Gln Ser Ser Asp Phe Pro Pro Ser Leu Thr Gln Pro 370 375 380 Ala Pro Asp Gln Ser Ser Thr Ile Gln Leu His Pro Ala Thr Ser Pro 385 390 395 400 Ala Val Ser Pro Thr Thr Ser Pro Ala Val Ser Leu Val Val Ser Pro 405 410 415 Ala Ala Ser Pro Glu Ile Ser Pro Glu Val Cys Pro Ala Ala Ser Thr 420 425 430 Val Val Ser Pro Ala Val Phe Ser Val Val Ser Pro Ala Ser Ser Ala 435 440 445 Val Leu Pro Ala Val Ser Leu Glu Val Pro Leu Thr Ala Ser Val Thr 450 455 460 Ser Pro Lys Ala Ser Pro Val Thr Ser Pro Ala Ala Ala Phe Pro Thr 465 470 475 480 Ala Ser Pro Ala Asn Lys Asp Val Ser Ser Phe Leu Glu Thr Thr Ala 485 490 495 Asp Val Glu Glu Ile Thr Gly Glu Gly Leu Thr Ala Ser Gly Ser Gly 500 505 510 Asp Val Met Arg Arg Arg Ile Ala Thr Pro Glu Glu Val Arg Leu Pro 515 520 525 Leu Gln His Gly Trp Arg Arg Glu Val Arg Ile Lys Lys Gly Ser His 530 535 540 Arg Trp Gln Gly Glu Thr Trp Tyr Tyr Gly Pro Cys Gly Lys Arg Met 545 550 555 560 Lys Gln Phe Pro Glu Val Ile Lys Tyr Leu Ser Arg Asn Leu Val His 565 570 575 Ser Val Arg Arg Glu His Phe Ser Phe Ser Pro Arg Met Pro Val Gly 580 585 590 Asp Phe Phe Glu Glu Arg Asp Thr Pro Glu Gly Leu Gln Trp Val Gln 595 600 605 Leu Ser Ala Glu Glu Ile Pro Ser Arg Ile Gln Ala Ile Thr Gly Lys 610 615 620 Arg Gly Arg Pro Arg Asn Thr Glu Lys Ala Lys Thr Lys Glu Val Pro 625 630 635 640 Lys Val Lys Arg Gly Arg Gly Arg Pro Pro Lys Val Lys Ile Thr Glu 645 650 655 Leu Leu Asn Lys Thr Asp Asn Arg Pro Leu Lys Lys Leu Glu Ala Gln 660 665 670 Glu Thr Leu Asn Glu Glu Asp Lys Ala Lys Ile Ala Lys Ser Lys Lys 675 680 685 Lys Met Arg Gln Lys Val Gln Arg Gly Glu Cys Leu Thr Thr Ile Gln 690 695 700 Gly Gln Ala Arg Asn Lys Arg Lys Gln Glu Thr Lys Ser Leu Lys His 705 710 715 720 Lys Glu Ala Lys Lys Lys Ser Xaa Ala Glu Lys Glu Lys Gly Lys Thr 725 730 735 Lys Gln Glu Lys Leu Lys Glu Lys Val Lys Arg Glu Lys Lys Glu Lys 740 745 750 Val Lys Met Lys Glu Lys Glu Glu Val Thr Lys Ala Lys Pro Ala Cys 755 760 765 Lys Ala Asp Lys Thr Leu Ala Thr Gln Arg Arg Leu Glu Glu Arg Gln 770 775 780 Lys Gln Gln Met Ile Leu Glu Glu Met Lys Lys Pro Thr Glu Asp Met 785 790 795 800 Cys Leu Thr Asp His Gln Pro Leu Pro Asp Phe Ser Arg Val Pro Gly 805 810 815 Leu Thr Leu Pro Ser Gly Ala Phe Ser Asp Cys Leu Thr Ile Val Glu 820 825 830 Phe Leu His Ser Phe Gly Lys Val Leu Gly Phe Asp Pro Ala Lys Asp 835 840 845 Val Pro Ser Leu Gly Val Leu Gln Glu Gly Leu Leu Cys Gln Gly Asp 850 855 860 Ser Leu Gly Glu Val Gln Asp Leu Leu Val Arg Leu Leu Lys Ala Ala 865 870 875 880 Leu His Asp Pro Gly Phe Pro Ser Tyr Cys Gln Ser Leu Lys Ile Leu 885 890 895 Gly Glu Lys Val Ser Glu Ile Pro Leu Thr Arg Asp Asn Val Ser Glu 900 905 910 Ile Leu Arg Cys Phe Leu Met Ala Tyr Gly Val Xaa Pro Ala Leu Cys 915 920 925 Asp Arg Leu Arg Thr Gln Pro Phe Gln Ala Gln Pro Pro Gln Gln Lys 930 935 940 Ala Ala Val Leu Ala Phe Pro Val His Glu Leu Asn Gly Ser Thr Leu 945 950 955 960 Ile Ile Asn Glu Ile Asp Lys Thr Leu Glu Ser Met Ser Ser Tyr Arg 965 970 975 Lys Asn Lys Trp Ile Val Glu Gly Arg Leu Arg Arg Leu Lys Thr Val 980 985 990 Leu Ala Lys Arg Thr Gly Arg Ser Glu Val Glu Met Gly Arg Pro Glu 995 1000 1005 Glu Cys Leu Gly Arg Arg Arg Ser Ser Arg Ile Met Glu Glu Thr Ser 1010 1015 1020 Gly Met Glu Glu Glu Glu Glu Glu Glu Ser Ile Ala Ala Val Pro Gly 1025 1030 1035 1040 Arg Arg Gly Arg Arg Asp Gly Glu Val Asp Ala Thr Ala Ser Ser Ile 1045 1050 1055 Pro Glu Leu Glu Arg Gln Ile Glu Lys Leu Ser Lys Arg Gln Leu Phe 1060 1065 1070 Phe Arg Lys Lys Leu Leu His Ser Ser Gln Met Leu Arg Ala Val Ser 1075 1080 1085 Leu Gly Gln Asp Arg Tyr Arg Arg Arg Tyr Trp Val Leu Pro Tyr Leu 1090 1095 1100 Ala Gly Ile Phe Val Glu Gly Thr Glu Gly Asn Leu Val Pro Glu Glu 1105 1110 1115 1120 Val Ile Lys Lys Glu Thr Asp Ser Leu Lys Val Ala Ala His Ala Ser 1125 1130 1135 Leu Asn Pro Ala Leu Phe Ser Met Lys Met Glu Leu Ala Gly Ser Asn 1140 1145 1150 Thr Thr Ala Ser Ser Pro Ala Arg Ala Arg Ser Arg Pro Leu Lys Thr 1155 1160 1165 Lys Pro Gly Phe Met Gln Pro Arg His Phe Lys Ser Pro Val Arg Gly 1170 1175 1180 Gln Asp Ser Glu Gln Pro Gln Ala Gln Leu Gln Pro Glu Ala Gln Leu 1185 1190 1195 1200 His Val Pro Ala Gln Pro Gln Pro Gln Leu Gln Leu Gln Leu Gln Ser 1205 1210 1215 His Lys Gly Phe Leu Glu Gln Glu Gly Ser Pro Leu Ser Leu Gly Gln 1220 1225 1230 Ser Gln His Asp Leu Ser Gln Ser Ala Phe Leu Ser Trp Leu Ser Gln 1235 1240 1245 Thr Gln Ser His Ser Ser Leu Leu Ser Ser Ser Val Leu Thr Pro Asp 1250 1255 1260 Ser Ser Pro Gly Lys Leu Asp Pro Ala Pro Ser Gln Pro Pro Glu Glu 1265 1270 1275 1280 Pro Glu Pro Asp Glu Ala Glu Ser Ser Pro Asp Leu Gln Ala Phe Trp 1285 1290 1295 Phe Asn Ile Ser Ala Gln Met Pro Cys Asn Ala Ala Pro Thr Pro Pro 1300 1305 1310 Leu Ala Val Ser Glu Asp Gln Pro Thr Pro Ser Pro Gln Gln Leu Ala 1315 1320 1325 Ser Ser Lys Pro Met Asn Arg Pro Ser Ala Ala Asn Pro Cys Ser Pro 1330 1335 1340 Val Gln Phe Ser Ser Thr Pro Leu Ala Gly Leu Ala Pro Lys Arg Arg 1345 1350 1355 1360 Ala Gly Asp Pro Gly Glu Met Pro Gln Ser Pro Thr Gly Leu Gly Gln 1365 1370 1375 Pro Lys Arg Arg Gly Arg Pro Pro Ser Lys Phe Phe Lys Gln Met Glu 1380 1385 1390 Gln Arg Tyr Leu Thr Gln Leu Thr Ala Gln Pro Val Pro Pro Glu Met 1395 1400 1405 Cys Ser Gly Trp Trp Trp Ile Pro Asp Pro Glu Met Leu Asp Ala Met 1410 1415 1420 Leu Lys Ala Leu His Pro Arg Gly Ile Arg Glu Lys Ala Leu His Lys 1425 1430 1435 1440 His Leu Asn Lys His Arg Asp Phe Leu Gln Glu Val Cys Leu Arg Pro 1445 1450 1455 Ser Ala Asp Pro Ile Phe Glu Pro Arg Gln Leu Pro Ala Phe Gln Glu 1460 1465 1470 Gly Ile Met Ser Trp Ser Pro Lys Glu Lys Thr Tyr Glu Thr Asp Leu 1475 1480 1485 Ala Val Leu Gln Trp Val Glu Glu Leu Glu Gln Arg Val Ile Met Ser 1490 1495 1500 Asp Leu Gln Ile Arg Gly Trp Thr Cys Pro Ser Pro Asp Ser Thr Arg 1505 1510 1515 1520 Glu Asp Leu Ala Tyr Cys Glu His Leu Ser Asp Ser Gln Glu Asp Ile 1525 1530 1535 Thr Trp Arg Gly Pro Gly Arg Glu Gly Leu Ala Pro Gln Arg Lys Thr 1540 1545 1550 Thr Asn Pro Leu Asp Leu Ala Val Met Arg Leu Ala Ala Leu Glu Gln 1555 1560 1565 Asn Val Lys Arg Arg Tyr Leu Arg Glu Pro Leu Trp Pro Thr His Glu 1570 1575 1580 Val Val Leu Glu Lys Ala Leu Leu Ser Thr Pro Asn Gly Ala Pro Glu 1585 1590 1595 1600 Gly Thr Thr Thr Glu Ile Ser Tyr Glu Ile Thr Pro Arg Ile Arg Ile 1605 1610 1615 Trp Arg Gln Thr Leu Gln Arg Cys Arg Ser Ala Ala His Val Cys Leu 1620 1625 1630 Cys Leu Gly His Leu Glu Arg Ser Ile Ala Trp Glu Lys Ser Val Asn 1635 1640 1645 Lys Val Thr Cys Leu Val Cys Arg Lys Gly Asp Asn Asp Glu Phe Leu 1650 1655 1660 Leu Leu Cys Asp Gly Cys Asp Arg Gly Cys His Ile Tyr Cys His Arg 1665 1670 1675 1680 Pro Lys Met Glu Ala Val Pro Glu Gly Asp Trp Phe Cys Thr Val Cys 1685 1690 1695 Leu Ala Gln Gln Val Glu Gly Glu Phe Thr Gln Lys Pro Gly Phe Pro 1700 1705 1710 Lys Arg Gly Gln Lys Arg Lys Ser Gly Tyr Ser Leu Asn Phe Ser Glu 1715 1720 1725 Gly Asp Gly Arg Arg Arg Arg Val Leu Leu Lys Gly Arg Glu Ser Pro 1730 1735 1740 Ala Ala Gly Pro Arg Tyr Ser Glu Glu Arg Leu Ser Pro Ser Lys Arg 1745 1750 1755 1760 Arg Arg Leu Ser Met Arg Asn His His Ser Asp Leu Thr Phe Cys Glu 1765 1770 1775 Ile Ile Leu Met Glu Met Glu Ser His Asp Ala Ala Trp Pro Phe Xaa 1780 1785 1790 Glu Pro Val Asn Pro Arg Leu Val Ser Gly Tyr Arg Arg Ile Ile Lys 1795 1800 1805 Asn Pro Met Asp Phe Ser Thr Met Arg Glu Arg Leu Leu Arg Gly Gly 1810 1815 1820 Tyr Thr Ser Ser Glu Glu Phe Ala Ala Asp Ala Leu Leu Val Phe Asp 1825 1830 1835 1840 Asn Cys Gln Thr Phe Asn Glu Asp Asp Ser Glu Val Gly Lys Ala Gly 1845 1850 1855 His Ile Met Arg Arg Phe Phe Glu Ser Arg Trp Glu Glu Phe Tyr Gln 1860 1865 1870 Gly Lys Gln Ala Asn Leu 1875 14 9408 DNA Homo sapiens CDS (740)...(6373) misc_feature (1)...(9408) n = A,T,C or G 14 gttccactca cagatttctt cttattgccc aggcttgagt gcaatgacct gttctcagct 60 tactcaacct ctgcctcttg ggtttcagtg atttttctgc ctcggcctcc tgagtagcta 120 agggaggagt cttgagatta tcatccacgg agggtggaag aggagagggt ggaaggggaa 180 taagaagaca ttcgggaggt gtcttgaggc tcagggagtt atcagttata gaatgttgtt 240 gagttggagg aagtggctgg cggcccatcc tgttttttaa agtttcacct gtgaagtagg 300 gccagtaggg caatcctgaa gaatgacgat gctccgctgc cgccattctg acctgtaagg 360 ccgaaagaaa gggaatgttt tcacacatat tcatttgatg gacaaaatta ccgccaccaa 420 cacggtctgc accttctgtt gctggtgata aatttttgca cctttccatc ctccaggttt 480 caaaatagca gtatcagtgt cataatatca cccttccact gagtactgcc gacagctggg 540 gagtaaaaaa aagtcattgg gacatcaccc tacagcagtt caggctgtgt ggttcgcaag 600 aagcatacac tggctttttg attcttgcta gttcccagct cacagtttgg gaggatccaa 660 caccaacctt tacgtgaagt ggaggcccaa ggacagtgag gagctgggtg gtcccagcct 720 ggagctgtgc cagcctgac atg gaa atg gag gca aac gag gca aac gac cat 772 Met Glu Met Glu Ala Asn Glu Ala Asn Asp His 1 5 10 ttt aac ttt act ggc ctt ccc cct gca cct gct gcc tca gga ctg aaa 820 Phe Asn Phe Thr Gly Leu Pro Pro Ala Pro Ala Ala Ser Gly Leu Lys 15 20 25 ccc tct cct tcc tca ggg gag ggc ctc tac act aac ggg tct ccc atg 868 Pro Ser Pro Ser Ser Gly Glu Gly Leu Tyr Thr Asn Gly Ser Pro Met 30 35 40 aac ttc ccc cag caa ggg aaa agt ttg aat ggg gat gtg aat gtt aat 916 Asn Phe Pro Gln Gln Gly Lys Ser Leu Asn Gly Asp Val Asn Val Asn 45 50 55 ggc tta tct act gta tct cac act act act tca ggg att ttg aac tct 964 Gly Leu Ser Thr Val Ser His Thr Thr Thr Ser Gly Ile Leu Asn Ser 60 65 70 75 gct ccc cac tcc tcc agc acc tca cac ctc cat cac ccc agc gtg gcc 1012 Ala Pro His Ser Ser Ser Thr Ser His Leu His His Pro Ser Val Ala 80 85 90 tac gac tgt ctc tgg aac tac tca cag tac cca tct gcc aat cct ggc 1060 Tyr Asp Cys Leu Trp Asn Tyr Ser Gln Tyr Pro Ser Ala Asn Pro Gly 95 100 105 agc aac ctc aag gac cca ccc ctt ctc tcc cag ttc tcg ggg gga caa 1108 Ser Asn Leu Lys Asp Pro Pro Leu Leu Ser Gln Phe Ser Gly Gly Gln 110 115 120 tac cca ctc aac ggc atc ctt ggg ggc agc cgg caa cct tca tcc cca 1156 Tyr Pro Leu Asn Gly Ile Leu Gly Gly Ser Arg Gln Pro Ser Ser Pro 125 130 135 agt cat aac act aac ctt cgg gct ggg agc caa aag ttc tgg gcc aac 1204 Ser His Asn Thr Asn Leu Arg Ala Gly Ser Gln Lys Phe Trp Ala Asn 140 145 150 155 ggt acc cat agt ccc atg ggg ctt aac ttt gat tca caa gaa ctg tat 1252 Gly Thr His Ser Pro Met Gly Leu Asn Phe Asp Ser Gln Glu Leu Tyr 160 165 170 gat tcc ttt cct gac cag aat ttt gag gag gta tgc agt ggt atc cat 1300 Asp Ser Phe Pro Asp Gln Asn Phe Glu Glu Val Cys Ser Gly Ile His 175 180 185 cct gat gag gca gca gaa aaa gag atg act tcc gtt gtg gca gaa aat 1348 Pro Asp Glu Ala Ala Glu Lys Glu Met Thr Ser Val Val Ala Glu Asn 190 195 200 ggc act ggc ttg gta tgc agc ttg gag ctg gaa gaa naa cag cca gaa 1396 Gly Thr Gly Leu Val Cys Ser Leu Glu Leu Glu Glu Xaa Gln Pro Glu 205 210 215 ctg aag atg tgt ggc tac aat ggc tct gtc cct tct gtg gaa tcg tta 1444 Leu Lys Met Cys Gly Tyr Asn Gly Ser Val Pro Ser Val Glu Ser Leu 220 225 230 235 cac caa gag gtc tca gtc ctg gtc cct gac ccc aca gtg agc tgt tta 1492 His Gln Glu Val Ser Val Leu Val Pro Asp Pro Thr Val Ser Cys Leu 240 245 250 gat gat cct tca cat ctt cct gat caa ctg gaa gac act cca atc ctc 1540 Asp Asp Pro Ser His Leu Pro Asp Gln Leu Glu Asp Thr Pro Ile Leu 255 260 265 agt gaa gac tct ctg gag ccc ttc aac tct ctg gca cca gag cca gtg 1588 Ser Glu Asp Ser Leu Glu Pro Phe Asn Ser Leu Ala Pro Glu Pro Val 270 275 280 agt gga gga cta tat ggt att gat gac acg gag ctg atg ggt gca gaa 1636 Ser Gly Gly Leu Tyr Gly Ile Asp Asp Thr Glu Leu Met Gly Ala Glu 285 290 295 gac aag ctg cct ctt gan gac agc cct gtg att tct gcc ctt gat tgc 1684 Asp Lys Leu Pro Leu Xaa Asp Ser Pro Val Ile Ser Ala Leu Asp Cys 300 305 310 315 cct tcc ctc aat aat gct act gcc ttc agt ctc ctg gca gat gat agt 1732 Pro Ser Leu Asn Asn Ala Thr Ala Phe Ser Leu Leu Ala Asp Asp Ser 320 325 330 caa aca tca act tct atc ttt gcc agt ccc act tct cca cct gtc cta 1780 Gln Thr Ser Thr Ser Ile Phe Ala Ser Pro Thr Ser Pro Pro Val Leu 335 340 345 ggg gag tct gtc ctg caa gat aac agc ttt gac ctg aat aat ggt agt 1828 Gly Glu Ser Val Leu Gln Asp Asn Ser Phe Asp Leu Asn Asn Gly Ser 350 355 360 gac gct gaa cag gaa gaa atg gaa act caa tct tca gac ttc cca cca 1876 Asp Ala Glu Gln Glu Glu Met Glu Thr Gln Ser Ser Asp Phe Pro Pro 365 370 375 tcc ctg acc cag cca gct cct gat cag tca tcc act att cag cta cat 1924 Ser Leu Thr Gln Pro Ala Pro Asp Gln Ser Ser Thr Ile Gln Leu His 380 385 390 395 cca gca acc tca cca gca gtc tcg cca aca acc tcc cca gca gtc tcc 1972 Pro Ala Thr Ser Pro Ala Val Ser Pro Thr Thr Ser Pro Ala Val Ser 400 405 410 cta gtg gtt tct cca gca gcc tcc cca gaa atc tct cca gaa gtt tgt 2020 Leu Val Val Ser Pro Ala Ala Ser Pro Glu Ile Ser Pro Glu Val Cys 415 420 425 ccc gca gct tct aca gtt gtc tct cca gca gtc ttc tca gtg gtc tct 2068 Pro Ala Ala Ser Thr Val Val Ser Pro Ala Val Phe Ser Val Val Ser 430 435 440 cca gct tct tca gca gtc ctc cca gca gtc tcc tta gaa gtc ccg ttg 2116 Pro Ala Ser Ser Ala Val Leu Pro Ala Val Ser Leu Glu Val Pro Leu 445 450 455 acg gct tca gtg aca tcc cca aaa gcc tct ccc gta act tcc cca gca 2164 Thr Ala Ser Val Thr Ser Pro Lys Ala Ser Pro Val Thr Ser Pro Ala 460 465 470 475 gct gcc ttt cca aca gcc tcc cca gca aat aag gat gtc agc agc ttt 2212 Ala Ala Phe Pro Thr Ala Ser Pro Ala Asn Lys Asp Val Ser Ser Phe 480 485 490 cta gaa acc act gct gac gtg gaa gag atc act gga gaa gga ctc act 2260 Leu Glu Thr Thr Ala Asp Val Glu Glu Ile Thr Gly Glu Gly Leu Thr 495 500 505 gct tct ggt agt ggt gat gtc atg agg aga cgt att gct acc cca gaa 2308 Ala Ser Gly Ser Gly Asp Val Met Arg Arg Arg Ile Ala Thr Pro Glu 510 515 520 gaa gtt cgt ctt ccc ctc caa cat ggg tgg cgg aga gag gtg cgc atc 2356 Glu Val Arg Leu Pro Leu Gln His Gly Trp Arg Arg Glu Val Arg Ile 525 530 535 aag aag ggc agc cac cga tgg cag ggg gag acn tgg tat tat ggc ccc 2404 Lys Lys Gly Ser His Arg Trp Gln Gly Glu Thr Trp Tyr Tyr Gly Pro 540 545 550 555 tgt ggg aag agg atg aag caa ttt cca gaa gtg atc aag tac ctg agc 2452 Cys Gly Lys Arg Met Lys Gln Phe Pro Glu Val Ile Lys Tyr Leu Ser 560 565 570 cgc aac ctg gta cac agt gtc cgc cga gag cac ttc agc ttc agt ccc 2500 Arg Asn Leu Val His Ser Val Arg Arg Glu His Phe Ser Phe Ser Pro 575 580 585 cgt atg cct gtt gga gat ttc ttt gaa gaa aga gac acg cca gag ggc 2548 Arg Met Pro Val Gly Asp Phe Phe Glu Glu Arg Asp Thr Pro Glu Gly 590 595 600 ttg cag tgg gtg cag ctc tca gca gag gag atc ccg tcg agg att cag 2596 Leu Gln Trp Val Gln Leu Ser Ala Glu Glu Ile Pro Ser Arg Ile Gln 605 610 615 gca att act ggc aaa cgg ggt cga cct cga aac act gag aag gct aag 2644 Ala Ile Thr Gly Lys Arg Gly Arg Pro Arg Asn Thr Glu Lys Ala Lys 620 625 630 635 act aag gaa gtc ccc aag gtg aaa cgg ggt cga ggt cgg cca cct aag 2692 Thr Lys Glu Val Pro Lys Val Lys Arg Gly Arg Gly Arg Pro Pro Lys 640 645 650 gtc aaa atc act gag cta ttg aac aag aca gac aac cgc ccc cta aag 2740 Val Lys Ile Thr Glu Leu Leu Asn Lys Thr Asp Asn Arg Pro Leu Lys 655 660 665 aaa ctg gag gcc caa gaa aca ttg aat gag gag gat aaa gca aag att 2788 Lys Leu Glu Ala Gln Glu Thr Leu Asn Glu Glu Asp Lys Ala Lys Ile 670 675 680 gct aaa agc aag aag aag atg agg cag aag gtt caa cgg gga gag tgt 2836 Ala Lys Ser Lys Lys Lys Met Arg Gln Lys Val Gln Arg Gly Glu Cys 685 690 695 ctn act act atc caa ggg cag gcc aga aat aag cgg aaa caa gag acc 2884 Leu Thr Thr Ile Gln Gly Gln Ala Arg Asn Lys Arg Lys Gln Glu Thr 700 705 710 715 aag agc tta aag cac aag gaa gct aag aag aaa tcc nag gct gag aaa 2932 Lys Ser Leu Lys His Lys Glu Ala Lys Lys Lys Ser Xaa Ala Glu Lys 720 725 730 gaa aaa gga aag aca aag cag gaa aaa ctg aag gaa aaa gtc aag agg 2980 Glu Lys Gly Lys Thr Lys Gln Glu Lys Leu Lys Glu Lys Val Lys Arg 735 740 745 gaa aag aag gag aag gtt aaa atg aag gaa aag gag gag gtg acc aaa 3028 Glu Lys Lys Glu Lys Val Lys Met Lys Glu Lys Glu Glu Val Thr Lys 750 755 760 gcc aag cca gcc tgt aaa gca gat aag acc ctg gcc aca cag agg cgc 3076 Ala Lys Pro Ala Cys Lys Ala Asp Lys Thr Leu Ala Thr Gln Arg Arg 765 770 775 ttg gag gaa cgg cag aag cag cag atg atc ttg gag gaa atg aag aag 3124 Leu Glu Glu Arg Gln Lys Gln Gln Met Ile Leu Glu Glu Met Lys Lys 780 785 790 795 ccg aca gag gat atg tgt ctg act gac cac cag ccc ctg cct gac ttc 3172 Pro Thr Glu Asp Met Cys Leu Thr Asp His Gln Pro Leu Pro Asp Phe 800 805 810 tca cga gtc cct ggt ctg aca ttg ccc agt gga gcc ttc tca gac tgc 3220 Ser Arg Val Pro Gly Leu Thr Leu Pro Ser Gly Ala Phe Ser Asp Cys 815 820 825 ttg acc att gtg gag ttc ctg cat agc ttt ggc aag gtg ctg ggc ttt 3268 Leu Thr Ile Val Glu Phe Leu His Ser Phe Gly Lys Val Leu Gly Phe 830 835 840 gat cct gcc aaa gat gtg cct agc ctg ggg gtc ctg cag gag gga ctc 3316 Asp Pro Ala Lys Asp Val Pro Ser Leu Gly Val Leu Gln Glu Gly Leu 845 850 855 ctg tgt caa ggt gac agc ttg ggt gag gtg caa gac ctg ctg gtc agg 3364 Leu Cys Gln Gly Asp Ser Leu Gly Glu Val Gln Asp Leu Leu Val Arg 860 865 870 875 ctg ctg aag gct gca ctc cat gat cct ggc ttt ccc tcc tac tgt cag 3412 Leu Leu Lys Ala Ala Leu His Asp Pro Gly Phe Pro Ser Tyr Cys Gln 880 885 890 tcc cta aag atc ttg ggg gag aag gtg tct gaa atc cca ctg aca aga 3460 Ser Leu Lys Ile Leu Gly Glu Lys Val Ser Glu Ile Pro Leu Thr Arg 895 900 905 gac aat gtg tca gag atc ctg cgc tgc ttc ctt atg gca tat gga gta 3508 Asp Asn Val Ser Glu Ile Leu Arg Cys Phe Leu Met Ala Tyr Gly Val 910 915 920 nag cca gcc ctc tgt gac cgc ctg cgc acc cag cct ttt cag gcc cag 3556 Xaa Pro Ala Leu Cys Asp Arg Leu Arg Thr Gln Pro Phe Gln Ala Gln 925 930 935 cca ccc cag cag aag gct gct gtc ctg gcc ttc cct gtg cat gag ctc 3604 Pro Pro Gln Gln Lys Ala Ala Val Leu Ala Phe Pro Val His Glu Leu 940 945 950 955 aat ggc tcc acc ctc atc atc aat gag att gac aag act ctg gag agt 3652 Asn Gly Ser Thr Leu Ile Ile Asn Glu Ile Asp Lys Thr Leu Glu Ser 960 965 970 atg tcc agc tac agg aaa aac aag tgg att gtt gaa ggc cgg ctc cgg 3700 Met Ser Ser Tyr Arg Lys Asn Lys Trp Ile Val Glu Gly Arg Leu Arg 975 980 985 agg ctg aaa act gtt ctg gcc aag cga act ggg cgg tct gaa gta gag 3748 Arg Leu Lys Thr Val Leu Ala Lys Arg Thr Gly Arg Ser Glu Val Glu 990 995 1000 atg gga agg cca gag gaa tgc ctg gga cgg agg cgc agt tct cgg atc 3796 Met Gly Arg Pro Glu Glu Cys Leu Gly Arg Arg Arg Ser Ser Arg Ile 1005 1010 1015 atg gag gag acc agt ggc atg gaa gaa gag gaa gaa gag gag tct ata 3844 Met Glu Glu Thr Ser Gly Met Glu Glu Glu Glu Glu Glu Glu Ser Ile 1020 1025 1030 1035 gca gct gtc cct ggc cgc agg ggt cga aga gat gga gag gtt gat gcc 3892 Ala Ala Val Pro Gly Arg Arg Gly Arg Arg Asp Gly Glu Val Asp Ala 1040 1045 1050 aca gca tct agc atc cca gag cta gag cgc cag ata gaa aaa ctc agc 3940 Thr Ala Ser Ser Ile Pro Glu Leu Glu Arg Gln Ile Glu Lys Leu Ser 1055 1060 1065 aag cgt cag ctt ttc ttt cgc aaa aag ctg ctt cac tca tcc cag atg 3988 Lys Arg Gln Leu Phe Phe Arg Lys Lys Leu Leu His Ser Ser Gln Met 1070 1075 1080 ctt cgg gcg gtc tcc ctg ggt cag gac cgc tac aga cgt cgc tac tgg 4036 Leu Arg Ala Val Ser Leu Gly Gln Asp Arg Tyr Arg Arg Arg Tyr Trp 1085 1090 1095 gta ttg ccg tat ttg gct ggt atc ttt gta gaa gga aca gag ggg aac 4084 Val Leu Pro Tyr Leu Ala Gly Ile Phe Val Glu Gly Thr Glu Gly Asn 1100 1105 1110 1115 tta gtt cct gag gag gtg ata aag aag gaa act gac tcc tta aaa gtg 4132 Leu Val Pro Glu Glu Val Ile Lys Lys Glu Thr Asp Ser Leu Lys Val 1120 1125 1130 gca gcc cat gcg tca ctc aac cct gcc ctc ttc tct atg aag atg gag 4180 Ala Ala His Ala Ser Leu Asn Pro Ala Leu Phe Ser Met Lys Met Glu 1135 1140 1145 tta gct ggc tcc aac acc act gcc agt tct cct gcc cgg gcc cga agc 4228 Leu Ala Gly Ser Asn Thr Thr Ala Ser Ser Pro Ala Arg Ala Arg Ser 1150 1155 1160 cga cct cta aaa act aag ccc ggg ttt atg caa cct agg cat ttt aag 4276 Arg Pro Leu Lys Thr Lys Pro Gly Phe Met Gln Pro Arg His Phe Lys 1165 1170 1175 tcc cct gtc agg ggt cag gat tca gaa cag ccc cag gcc cag ctt cag 4324 Ser Pro Val Arg Gly Gln Asp Ser Glu Gln Pro Gln Ala Gln Leu Gln 1180 1185 1190 1195 cct gag gct cag ctt cat gtt cct gcc cag ccc cag cct cag ctt cag 4372 Pro Glu Ala Gln Leu His Val Pro Ala Gln Pro Gln Pro Gln Leu Gln 1200 1205 1210 ctt cag ctt cag tcc cat aag ggg ttc ctg gag caa gaa ggc tcc cct 4420 Leu Gln Leu Gln Ser His Lys Gly Phe Leu Glu Gln Glu Gly Ser Pro 1215 1220 1225 ttg tca ctg ggt cag agc cag cat gac ctc agc cag tca gcc ttc ctg 4468 Leu Ser Leu Gly Gln Ser Gln His Asp Leu Ser Gln Ser Ala Phe Leu 1230 1235 1240 tct tgg ctg agc cag act cag agc cat agc tcc ctg ttg agc agc tca 4516 Ser Trp Leu Ser Gln Thr Gln Ser His Ser Ser Leu Leu Ser Ser Ser 1245 1250 1255 gtc ctc aca cct gat agc agt ccg gga aaa cta gac cca gct cca tca 4564 Val Leu Thr Pro Asp Ser Ser Pro Gly Lys Leu Asp Pro Ala Pro Ser 1260 1265 1270 1275 caa ccc ccg gag gag cca gag cct gat gag gca gaa tcc agc cct gat 4612 Gln Pro Pro Glu Glu Pro Glu Pro Asp Glu Ala Glu Ser Ser Pro Asp 1280 1285 1290 ctt caa gca ttc tgg ttt aac atc tca gcc cag atg ccc tgc aat gct 4660 Leu Gln Ala Phe Trp Phe Asn Ile Ser Ala Gln Met Pro Cys Asn Ala 1295 1300 1305 gcc ccc aca ccg ccc ctt gca gtt tct gag gac caa ccc act ccc tcc 4708 Ala Pro Thr Pro Pro Leu Ala Val Ser Glu Asp Gln Pro Thr Pro Ser 1310 1315 1320 cct cag cag ctt gcc tcc tcc aag cca atg aat aga cct agt gct gcc 4756 Pro Gln Gln Leu Ala Ser Ser Lys Pro Met Asn Arg Pro Ser Ala Ala 1325 1330 1335 aac cct tgt tct cca gtg cag ttc tct tcc acg ccc ttg gct ggg ttg 4804 Asn Pro Cys Ser Pro Val Gln Phe Ser Ser Thr Pro Leu Ala Gly Leu 1340 1345 1350 1355 gcc cct aag agg cga gca gga gac cct gga gaa atg cca cag agt ccc 4852 Ala Pro Lys Arg Arg Ala Gly Asp Pro Gly Glu Met Pro Gln Ser Pro 1360 1365 1370 aca ggg ctg gga cag ccc aaa cgg aga ggg aga cct ccc agt aag ttc 4900 Thr Gly Leu Gly Gln Pro Lys Arg Arg Gly Arg Pro Pro Ser Lys Phe 1375 1380 1385 ttc aaa cag atg gaa cag cgt tac cta acc cag ctg aca gcc cag cct 4948 Phe Lys Gln Met Glu Gln Arg Tyr Leu Thr Gln Leu Thr Ala Gln Pro 1390 1395 1400 gtc cca cct gag atg tgc tca ggc tgg tgg tgg ata cca gat cct gag 4996 Val Pro Pro Glu Met Cys Ser Gly Trp Trp Trp Ile Pro Asp Pro Glu 1405 1410 1415 atg ttg gat gcc atg ctc aag gcc cta cac ccc cga ggt atc cgg gag 5044 Met Leu Asp Ala Met Leu Lys Ala Leu His Pro Arg Gly Ile Arg Glu 1420 1425 1430 1435 aag gca ctt cac aaa cac ctt aac aag cac agg gac ttc ttg cag gaa 5092 Lys Ala Leu His Lys His Leu Asn Lys His Arg Asp Phe Leu Gln Glu 1440 1445 1450 gtc tgc ctg cgg ccc tca gct gac ccc atc ttt gag ccc agg caa cta 5140 Val Cys Leu Arg Pro Ser Ala Asp Pro Ile Phe Glu Pro Arg Gln Leu 1455 1460 1465 cct gcc ttt caa gaa ggg att atg agc tgg tcc ccc aaa gag aag aca 5188 Pro Ala Phe Gln Glu Gly Ile Met Ser Trp Ser Pro Lys Glu Lys Thr 1470 1475 1480 tac gag aca gac cta gca gtg ctt caa tgg gta gag gag ctg gag cag 5236 Tyr Glu Thr Asp Leu Ala Val Leu Gln Trp Val Glu Glu Leu Glu Gln 1485 1490 1495 cgg gtt atc atg tct gat ctg cag att cgg ggc tgg aca tgt cct agc 5284 Arg Val Ile Met Ser Asp Leu Gln Ile Arg Gly Trp Thr Cys Pro Ser 1500 1505 1510 1515 cca gac tct acc cgt gaa gac ttg gcc tac tgt gag cac ctc tcc gac 5332 Pro Asp Ser Thr Arg Glu Asp Leu Ala Tyr Cys Glu His Leu Ser Asp 1520 1525 1530 tcc cag gag gat atc acc tgg cga ggt ccg ggc agg gag gga ctg gca 5380 Ser Gln Glu Asp Ile Thr Trp Arg Gly Pro Gly Arg Glu Gly Leu Ala 1535 1540 1545 cct caa cgt aaa act acc aac cct ttg gac ctg gct gtg atg cgg ctg 5428 Pro Gln Arg Lys Thr Thr Asn Pro Leu Asp Leu Ala Val Met Arg Leu 1550 1555 1560 gct gcc ctg gaa caa aat gta aaa cgg cgg tac ctg cgg gag ccc ctc 5476 Ala Ala Leu Glu Gln Asn Val Lys Arg Arg Tyr Leu Arg Glu Pro Leu 1565 1570 1575 tgg cca act cat gag gtt gtg ctg gag aaa gcc ctg ctt agc aca cct 5524 Trp Pro Thr His Glu Val Val Leu Glu Lys Ala Leu Leu Ser Thr Pro 1580 1585 1590 1595 aat ggt gcc cct gag ggc acc act aca gag ata tca tat gag atc acc 5572 Asn Gly Ala Pro Glu Gly Thr Thr Thr Glu Ile Ser Tyr Glu Ile Thr 1600 1605 1610 cct cgc att cgt atc tgg cgc cag acc ctc cag cgg tgc cgg agc gca 5620 Pro Arg Ile Arg Ile Trp Arg Gln Thr Leu Gln Arg Cys Arg Ser Ala 1615 1620 1625 gcc cat gtg tgc ttg tgc ctg ggc cat ctg gag agg tcc att gcc tgg 5668 Ala His Val Cys Leu Cys Leu Gly His Leu Glu Arg Ser Ile Ala Trp 1630 1635 1640 gag aag tct gtc aac aaa gtg aca tgt cta gtc tgc cgg aag ggt gac 5716 Glu Lys Ser Val Asn Lys Val Thr Cys Leu Val Cys Arg Lys Gly Asp 1645 1650 1655 aat gat gag ttt ctt ctg ctt tgt gat ggg tgt gac cgt ggc tgc cac 5764 Asn Asp Glu Phe Leu Leu Leu Cys Asp Gly Cys Asp Arg Gly Cys His 1660 1665 1670 1675 att tac tgc cat cgt ccc aag atg gag gct gtc cca gaa gga gat tgg 5812 Ile Tyr Cys His Arg Pro Lys Met Glu Ala Val Pro Glu Gly Asp Trp 1680 1685 1690 ttc tgt act gtc tgt ttg gct cag cag gtg gag gga gaa ttc act cag 5860 Phe Cys Thr Val Cys Leu Ala Gln Gln Val Glu Gly Glu Phe Thr Gln 1695 1700 1705 aag cct ggt ttc cca aag cgt ggc cag aag cgg aaa agt ggt tat tcg 5908 Lys Pro Gly Phe Pro Lys Arg Gly Gln Lys Arg Lys Ser Gly Tyr Ser 1710 1715 1720 ctg aac ttc tca gaa ggt gat ggc cgc cga cgc cgg gta ctg ttg aag 5956 Leu Asn Phe Ser Glu Gly Asp Gly Arg Arg Arg Arg Val Leu Leu Lys 1725 1730 1735 ggc cga gaa agc cca gca gca ggg cct cgg tac tcg gaa gaa agg ctc 6004 Gly Arg Glu Ser Pro Ala Ala Gly Pro Arg Tyr Ser Glu Glu Arg Leu 1740 1745 1750 1755 tcc ccc tcc aag cgg cgg cga ctc tct atg cgg aac cac cac agt gat 6052 Ser Pro Ser Lys Arg Arg Arg Leu Ser Met Arg Asn His His Ser Asp 1760 1765 1770 ctc aca ttt tgc gag att atc ctg atg gag atg gaa tcc cat gat gca 6100 Leu Thr Phe Cys Glu Ile Ile Leu Met Glu Met Glu Ser His Asp Ala 1775 1780 1785 gcc tgg cct ttc nta gag cct gtg aac cca cgt ttg gtg agt ggg tac 6148 Ala Trp Pro Phe Xaa Glu Pro Val Asn Pro Arg Leu Val Ser Gly Tyr 1790 1795 1800 cgg cgc atc atc aaa aat cct atg gat ttt tcc acc atg cgg gag cgg 6196 Arg Arg Ile Ile Lys Asn Pro Met Asp Phe Ser Thr Met Arg Glu Arg 1805 1810 1815 ctg ctc agg gga ggg tac acc agc tca gag gag ttt gcg gct gat gcc 6244 Leu Leu Arg Gly Gly Tyr Thr Ser Ser Glu Glu Phe Ala Ala Asp Ala 1820 1825 1830 1835 ctc ctg gta ttt gac aac tgc cag act ttc aac gag gat gac tct gaa 6292 Leu Leu Val Phe Asp Asn Cys Gln Thr Phe Asn Glu Asp Asp Ser Glu 1840 1845 1850 gta ggc aag gct ggg cac atc atg cgc cgc ttc ttc gag agc cgc tgg 6340 Val Gly Lys Ala Gly His Ile Met Arg Arg Phe Phe Glu Ser Arg Trp 1855 1860 1865 gag gag ttt tat cag gga aaa cag gcc aat ctg tgaggcaagg gaggtgggga 6393 Glu Glu Phe Tyr Gln Gly Lys Gln Ala Asn Leu 1870 1875 gtcaccttgt ggcatctccc cccaccttcc aaacaaaaac ctgccatttt cacctgctga 6453 tgctgccctg ggtccagact caagtcagat acaaccctga tttttgacct tgcccttggc 6513 agtgccccac atcctcttat tcctacatcc ctttctccct tccctcctct tgctcctcaa 6573 gtaagaggtg cagagaggag tccttctgga ctaaaagcca aaaaaagaaa gaaaaaaata 6633 atttttcttt tctgttttat ttgctaatta aaaatgggga gggggaaagt cgtccctact 6693 tcctcctccg tgcttcctct cctcccctgt acgtgcccca gcattctggg gttatttaac 6753 aatagcaata gttctagtga atgtgtgaaa ccaagaaaca ctctgtactg tgtgcggacc 6813 cgcagtgacg gccagtaaag tggacttaac tcccaagtgt gtcgcggccg gacaccgggc 6873 cctggacatg ctgcttccat gttcagtccc ttccctgctt ctcgctgtct ttcttttccc 6933 acctcccacc ccccagtttt cagattttct ctcatccaat aatgtaaaac tatcgtgtac 6993 gggttcctcc ctccttttct cttctcccaa atcttttccc ttcaaaggaa aaaaaaatgt 7053 tcagaggtcc ctgtcttctg tccccatctt cctgccgata gctatcccct gtatgatgtt 7113 ggatgctcct cacatgctga gtttccagcc ttttctgaaa ctcattagct ggggagaggg 7173 cagggaggct tcctgggcct tccaacctcc ttccccacct ccttcccaaa ccctcttggg 7233 aactcctcag ggacaactac tgctgagttt gggtgcaccc aaagatggag gccaagtagc 7293 aatggggccg gcctcacaga gagcgccgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg 7353 tccgccacac aacgcgctgt gtgtgtgtgt gtgtgtctca cacacacagc gcgcagtgtg 7413 tgtgtgtgtg tgtgtgtgta tgtgtgtgtg tgtgtgaccc tgtattgttt gataggatcc 7473 attcagtttc cccaagtacc tgttttcatt cccatttttc ccattgttta aaaccatcac 7533 ttttttgtct ttgggaaacc acaggaacaa tttctctgga gacaaggctg tgtctctctc 7593 ctggtcattt ttgttccagc ctcttcagac tgtgcatctt ttcagcagga actccctctc 7653 ttctcggtag ctttgaatct taagcttcta cgggagagtg gtagaactgg atcatttcat 7713 aatcccattt agttgtgctt ttcttcatat acttcatacc ccaggacccc ttccccagca 7773 gcagagaccc tggagcacag gagagtaggg aggaggggtt ctgggtccat cactgcctta 7833 catgtgacta tgtccaagtt aagcccccaa cacgagagga aagctgctga ctcccagcta 7893 tagccatggg cacttggccc cctgcttttc ctgctcagca gagcccctcc cttcagagat 7953 tacgggtact tgcactgggg aggtggctgc tggctggccc aagcagagag ctgaggcatc 8013 caagaaatgt tccattgggg ggtgggggtg ccaggtgagg tggagcattc cttgtattct 8073 ggcagcactg aagagccact gaagggggta ggggcagtgt aggtcctggg gcagcccctt 8133 tattccttta tgccccttct ccctcatagc ctatttctaa agtcgccttt tctgtcagat 8193 aaacctcaaa acttttaatt ttatttgaga tttttttttg cttttaagag gtggattgaa 8253 gaatatttga attgacttta tattatgcat aaatatttat attttatcta aataactgcg 8313 ctgtaacaaa ctttgtgtta gacagttgaa actgttagag ttgggggctc tgctttttcc 8373 ccctggcaat tttcccttgg tataagatgt gctagattaa tttcattgtg aggtggatgg 8433 gggagtgaaa ttgtgaggtg gatgggggag tgaaatctcc atggttcctg ctttgtgttc 8493 ctctcccagc tccatctctt tccctaggga ccaggcactc atatggcggg gtggggtcct 8553 agcctcagtt tgaagaagtg ggggctggag cggggttggg ggtggtaggg atagggcatg 8613 atcaaagggg ccatttcttg cttttctttc ctcatcttca ctgccccctt gagctaggtg 8673 gattttctct tcatgacaag agtatttggt agggaaagca ggtttaaaat aaaaagacaa 8733 cccaccccct gcccttttgc ttccctccca tcagtctggt tgacaggaag aaaccacacc 8793 atcaacacca acaagtttnt gtgttccttt tacagcaaaa gggacttttt atataaccaa 8853 atgtggtgtt ttagtgactt tttgataatg tacagttttt tgtgaattta aatttatttc 8913 tttctatatt tttaggacca atttcatttt taataaggtt aaaaagaaaa aaaaagtcta 8973 gcgaaaaaac tcctgttttt gccatgtgat gttccacaag tgcagctgta gaaaagtgct 9033 tgtcagttgt tgaataaaaa aaccacattt gatagagatt caaaagactc tgtgtattca 9093 tcttcccttc tacacacctg agggggagac ggcgttggga taggtatgac tggcttaaga 9153 gaccacaggc aagggaacaa caggggctcc tgttccatac cctctgtgtg ggatggaaag 9213 ggtcattagt gctcccgcct aaatgtctgg ctgagttgct ggaagcaaag gggggattca 9273 gtgcatccag gtcctgcctt gtgagatgtg gccccagctt cctaagctgc cacctctgtg 9333 ttcctgtcat agcaaatatg ggaccatcac cagcttacca cttcccactc acggataaga 9393 caccaagacg tagac 9408 15 24 DNA Artificial Sequence Synthetically generated primer 15 tgactctgaa gtaggcaagg ctgg 24 16 22 DNA Artificial Sequence Synthetically generated primer 16 cttgcctcac agattggcct gt 22 17 21 DNA Artificial Sequence Synthetically generated primer 17 ttgccgtatt tggctggtat c 21 18 23 DNA Artificial Sequence Synthetically generated primer 18 catagagaag agggcagggt tga 23 19 20 DNA Artificial Sequence Synthetically generated primer 19 cttttgagca agttcagcct 20 20 22 DNA Artificial Sequence Synthetically generated primer 20 gtcggcttct tcatttcctc ca 22 21 1972 PRT Homo sapiens 21 Met Gly Gln Thr Lys Ser Thr Ser Ser Gly Gly Gly Asn Arg Lys Cys 1 5 10 15 Asn Gln Glu Gln Ser Lys Asn Gln Pro Leu Asp Ala Arg Val Asp Lys 20 25 30 Ile Lys Asp Lys Lys Pro Arg Lys Lys Ala Met Glu Ser Ser Ser Asn 35 40 45 Ser Asp Ser Asp Ser Gly Thr Ser Ser Asp Thr Ser Ser Glu Gly Ile 50 55 60 Ser Ser Ser Asp Ser Asp Asp Leu Glu Glu Asp Glu Glu Glu Glu Asp 65 70 75 80 Gln Ser Ile Glu Glu Ser Glu Asp Asp Asp Ser Asp Ser Glu Ser Glu 85 90 95 Ala Gln His Lys Ser Asn Asn Gln Val Leu Leu His Gly Ile Ser Asp 100 105 110 Pro Lys Ala Asp Gly Gln Lys Ala Thr Glu Lys Ala Gln Glu Lys Arg 115 120 125 Ile His Gln Pro Leu Pro Leu Ala Phe Glu Ser Gln Thr His Ser Phe 130 135 140 Gln Ser Gln Gln Lys Gln Pro Gln Val Leu Ser Gln Gln Leu Pro Phe 145 150 155 160 Ile Phe Gln Ser Ser Gln Ala Lys Glu Glu Ser Val Asn Lys His Thr 165 170 175 Ser Val Ile Gln Ser Thr Gly Leu Val Ser Asn Val Lys Pro Leu Ser 180 185 190 Leu Val Asn Gln Ala Lys Lys Glu Thr Tyr Met Lys Leu Ile Val Pro 195 200 205 Ser Pro Asp Val Leu Lys Ala Gly Asn Lys Asn Thr Ser Glu Glu Ser 210 215 220 Ser Leu Leu Thr Ser Glu Leu Arg Ser Lys Arg Glu Gln Tyr Lys Gln 225 230 235 240 Ala Phe Pro Ser Gln Leu Lys Lys Gln Glu Ser Ser Lys Ser Leu Lys 245 250 255 Lys Val Ile Ala Ala Leu Ser Asn Pro Lys Ala Thr Ser Ser Ser Pro 260 265 270 Ala His Pro Lys Gln Thr Leu Glu Asn Asn His Pro Asn Pro Phe Leu 275 280 285 Thr Asn Ala Leu Leu Gly Asn His Gln Pro Asn Gly Val Ile Gln Ser 290 295 300 Val Ile Gln Glu Ala Pro Leu Ala Leu Thr Thr Lys Thr Lys Met Gln 305 310 315 320 Ser Lys Ile Asn Glu Asn Ile Ala Ala Ala Ser Ser Thr Pro Phe Ser 325 330 335 Ser Pro Val Asn Leu Ser Thr Ser Gly Arg Arg Thr Pro Gly Asn Gln 340 345 350 Thr Pro Val Met Pro Ser Ala Ser Pro Ile Leu His Ser Gln Gly Lys 355 360 365 Glu Lys Ala Val Ser Asn Asn Val Asn Pro Val Lys Thr Gln His His 370 375 380 Ser His Pro Ala Lys Ser Leu Val Glu Gln Phe Arg Gly Thr Asp Ser 385 390 395 400 Asp Ile Pro Ser Ser Lys Asp Ser Glu Asp Ser Asn Glu Asp Glu Glu 405 410 415 Glu Asp Asp Glu Glu Glu Asp Glu Glu Asp Asp Glu Asp Asp Glu Ser 420 425 430 Asp Asp Ser Gln Ser Glu Ser Asp Ser Asn Ser Glu Ser Asp Thr Glu 435 440 445 Gly Ser Glu Glu Glu Asp Asp Asp Asp Lys Asp Gln Asp Glu Ser Asp 450 455 460 Ser Asp Thr Glu Gly Glu Lys Thr Ser Met Lys Leu Asn Lys Thr Thr 465 470 475 480 Ser Ser Val Lys Ser Pro Ser Met Ser Leu Thr Gly His Ser Thr Pro 485 490 495 Arg Asn Leu His Ile Ala Lys Ala Pro Gly Ser Ala Pro Ala Ala Leu 500 505 510 Cys Ser Glu Ser Gln Ser Pro Ala Phe Leu Gly Thr Ser Ser Ser Thr 515 520 525 Leu Thr Ser Ser Pro His Ser Gly Thr Ser Lys Arg Arg Arg Val Thr 530 535 540 Asp Glu Arg Glu Leu Arg Ile Pro Leu Glu Tyr Gly Trp Gln Arg Glu 545 550 555 560 Thr Arg Ile Arg Asn Phe Gly Gly Arg Leu Gln Gly Glu Val Ala Tyr 565 570 575 Tyr Ala Pro Cys Gly Lys Lys Leu Arg Gln Tyr Pro Glu Val Ile Lys 580 585 590 Tyr Leu Ser Arg Asn Gly Ile Met Asp Ile Ser Arg Asp Asn Phe Ser 595 600 605 Phe Ser Ala Lys Ile Arg Val Gly Asp Phe Tyr Glu Ala Arg Asp Gly 610 615 620 Pro Gln Glu Met Gln Trp Cys Leu Leu Lys Glu Glu Asp Val Ile Pro 625 630 635 640 Arg Ile Arg Ala Met Glu Gly Arg Arg Gly Arg Pro Pro Asn Pro Asp 645 650 655 Arg Gln Arg Ala Arg Glu Glu Ser Arg Met Arg Arg Arg Lys Gly Arg 660 665 670 Pro Pro Asn Val Gly Asn Ala Glu Phe Leu Asp Asn Ala Asp Ala Lys 675 680 685 Leu Leu Arg Lys Leu Gln Ala Gln Glu Ile Ala Arg Gln Ala Ala Gln 690 695 700 Ile Lys Leu Leu Arg Lys Leu Gln Lys Gln Glu Gln Ala Arg Val Ala 705 710 715 720 Lys Glu Ala Lys Lys Gln Gln Ala Ile Met Ala Ala Glu Glu Lys Arg 725 730 735 Lys Gln Lys Glu Gln Ile Lys Ile Met Lys Gln Gln Glu Lys Ile Lys 740 745 750 Arg Ile Gln Gln Ile Arg Met Glu Lys Glu Leu Arg Ala Gln Gln Ile 755 760 765 Leu Glu Ala Lys Lys Lys Lys Lys Glu Glu Ala Ala Asn Ala Lys Leu 770 775 780 Leu Glu Ala Glu Lys Arg Ile Lys Glu Lys Glu Met Arg Arg Gln Gln 785 790 795 800 Ala Val Leu Leu Lys His Gln Glu Arg Glu Arg Arg Arg Gln His Met 805 810 815 Met Leu Met Lys Ala Met Glu Ala Arg Lys Lys Ala Glu Glu Lys Glu 820 825 830 Arg Leu Lys Gln Glu Lys Arg Asp Glu Lys Arg Leu Asn Lys Glu Arg 835 840 845 Lys Leu Glu Gln Arg Arg Leu Glu Leu Glu Met Ala Lys Glu Leu Lys 850 855 860 Lys Pro Asn Glu Asp Met Cys Leu Ala Asp Gln Lys Pro Leu Pro Glu 865 870 875 880 Leu Pro Arg Ile Pro Gly Leu Val Leu Ser Gly Ser Thr Phe Ser Asp 885 890 895 Cys Leu Met Val Val Gln Phe Leu Arg Asn Phe Gly Lys Val Leu Gly 900 905 910 Phe Asp Val Asn Ile Asp Val Pro Asn Leu Ser Val Leu Gln Glu Gly 915 920 925 Leu Leu Asn Ile Gly Asp Ser Met Gly Glu Val Gln Asp Leu Leu Val 930 935 940 Arg Leu Leu Ser Ala Ala Val Cys Asp Pro Gly Leu Ile Thr Gly Tyr 945 950 955 960 Lys Ala Lys Thr Ala Leu Gly Glu His Leu Leu Asn Val Gly Val Asn 965 970 975 Arg Asp Asn Val Ser Glu Ile Leu Gln Ile Phe Met Glu Ala His Cys 980 985 990 Gly Gln Thr Glu Leu Thr Glu Ser Leu Lys Thr Lys Ala Phe Gln Ala 995 1000 1005 His Thr Pro Ala Gln Lys Ala Ser Val Leu Ala Phe Leu Ile Asn Glu 1010 1015 1020 Leu Ala Cys Ser Lys Ser Val Val Ser Glu Ile Asp Lys Asn Ile Asp 1025 1030 1035 1040 Tyr Met Ser Asn Leu Arg Arg Asp Lys Trp Val Val Glu Gly Lys Leu 1045 1050 1055 Arg Lys Leu Arg Ile Ile His Ala Lys Lys Thr Gly Lys Arg Asp Thr 1060 1065 1070 Ser Gly Gly Ile Asp Leu Gly Glu Glu Gln His Pro Leu Gly Thr Pro 1075 1080 1085 Thr Pro Gly Arg Lys Arg Arg Arg Lys Gly Gly Asp Ser Asp Tyr Asp 1090 1095 1100 Asp Asp Asp Asp Asp Asp Ser Asp Asp Gln Gly Asp Glu Asp Asp Glu 1105 1110 1115 1120 Asp Glu Glu Asp Lys Glu Asp Gln Lys Gly Lys Lys Thr Asp Ile Cys 1125 1130 1135 Glu Asp Glu Asp Glu Gly Asp Gln Ala Ala Ser Val Glu Glu Leu Glu 1140 1145 1150 Lys Gln Ile Glu Lys Leu Ser Lys Gln Gln Ser Gln Tyr Arg Arg Lys 1155 1160 1165 Leu Phe Asp Ala Ser His Ser Leu Arg Ser Val Met Phe Gly Pro Asp 1170 1175 1180 Arg Tyr Arg Arg Arg Tyr Trp Ile Leu Pro Arg Cys Gly Gly Ile Phe 1185 1190 1195 1200 Val Glu Gly Met Glu Ser Gly Glu Gly Leu Glu Glu Ile Ala Lys Glu 1205 1210 1215 Arg Glu Lys Leu Lys Lys Ala Glu Ser Val Gln Ile Lys Glu Glu Met 1220 1225 1230 Phe Glu Thr Ser Gly Asp Ser Leu Asn Cys Ser Asn Thr Asp His Cys 1235 1240 1245 Glu Gln Lys Glu Asp Leu Lys Glu Lys Asp Asn Thr Asn Leu Phe Leu 1250 1255 1260 Gln Lys Pro Gly Ser Phe Ser Lys Leu Ser Lys Leu Leu Glu Val Ala 1265 1270 1275 1280 Lys Met Pro Pro Glu Ser Glu Val Met Thr Pro Lys Pro Asn Ala Gly 1285 1290 1295 Ala Asn Gly Cys Thr Leu Ser Tyr Gln Asn Ser Gly Lys His Ser Leu 1300 1305 1310 Gly Ser Val Gln Ser Thr Ala Thr Gln Ser Asn Val Glu Lys Ala Asp 1315 1320 1325 Ser Asn Asn Leu Phe Asn Thr Gly Ser Ser Gly Pro Gly Lys Phe Tyr 1330 1335 1340 Ser Pro Leu Pro Asn Asp Gln Leu Leu Lys Thr Leu Thr Glu Lys Asn 1345 1350 1355 1360 Arg Gln Trp Phe Ser Leu Leu Pro Arg Thr Pro Cys Asp Asp Thr Ser 1365 1370 1375 Leu Thr His Ala Asp Met Ser Thr Ala Ser Leu Val Thr Pro Gln Ser 1380 1385 1390 Gln Pro Pro Ser Lys Ser Pro Ser Pro Thr Pro Ala Pro Leu Gly Ser 1395 1400 1405 Ser Ala Gln Asn Pro Val Gly Leu Asn Pro Phe Ala Leu Ser Pro Leu 1410 1415 1420 Gln Val Lys Gly Gly Val Ser Met Met Gly Leu Gln Phe Cys Gly Trp 1425 1430 1435 1440 Pro Thr Gly Val Val Thr Ser Asn Ile Pro Phe Thr Leu Ser Val Pro 1445 1450 1455 Ser Leu Gly Ser Gly Leu Gly Leu Ser Glu Gly Asn Gly Asn Ser Phe 1460 1465 1470 Leu Thr Ser Asn Val Ala Ser Ser Lys Ser Glu Ser Pro Val Pro Gln 1475 1480 1485 Asn Glu Lys Ala Thr Ser Ala Gln Pro Ala Ala Val Glu Val Ala Lys 1490 1495 1500 Pro Val Asp Phe Pro Ser Pro Lys Pro Ile Pro Glu Glu Met Gln Phe 1505 1510 1515 1520 Gly Trp Trp Arg Ile Ile Asp Pro Glu Asp Leu Lys Ala Leu Leu Lys 1525 1530 1535 Val Leu His Leu Arg Gly Ile Arg Glu Lys Ala Leu Gln Lys Gln Ile 1540 1545 1550 Gln Lys His Leu Asp Tyr Ile Thr Gln Ala Cys Leu Lys Asn Lys Asp 1555 1560 1565 Val Ala Ile Ile Glu Leu Asn Glu Asn Glu Glu Asn Gln Val Thr Arg 1570 1575 1580 Asp Ile Val Glu Asn Trp Ser Val Glu Glu Gln Ala Met Glu Met Asp 1585 1590 1595 1600 Leu Ser Val Leu Gln Gln Val Glu Asp Leu Glu Arg Arg Val Ala Ser 1605 1610 1615 Ala Ser Leu Gln Val Lys Gly Trp Met Cys Pro Glu Pro Ala Ser Glu 1620 1625 1630 Arg Glu Asp Leu Val Tyr Phe Glu His Lys Ser Phe Thr Lys Leu Cys 1635 1640 1645 Lys Glu His Asp Gly Glu Phe Thr Gly Glu Asp Glu Ser Ser Ala His 1650 1655 1660 Ala Leu Glu Arg Lys Ser Asp Asn Pro Leu Asp Ile Ala Val Thr Arg 1665 1670 1675 1680 Leu Ala Asp Leu Glu Arg Asn Ile Glu Arg Arg Ile Glu Glu Asp Ile 1685 1690 1695 Ala Pro Gly Leu Arg Val Trp Arg Arg Ala Leu Ser Glu Ala Arg Ser 1700 1705 1710 Ala Ala Gln Val Ala Leu Cys Ile Gln Gln Leu Gln Lys Ser Ile Ala 1715 1720 1725 Trp Glu Lys Ser Ile Met Lys Val Tyr Cys Gln Ile Cys Arg Lys Gly 1730 1735 1740 Asp Asn Glu Glu Leu Leu Leu Leu Cys Asp Gly Cys Asp Lys Gly Cys 1745 1750 1755 1760 His Thr Tyr Cys His Arg Pro Lys Ile Thr Thr Ile Pro Asp Gly Asp 1765 1770 1775 Trp Phe Cys Pro Ala Cys Ile Ala Lys Ala Ser Gly Gln Thr Leu Lys 1780 1785 1790 Ile Lys Lys Leu His Val Lys Gly Lys Lys Thr Asn Glu Ser Lys Lys 1795 1800 1805 Gly Lys Lys Val Thr Leu Thr Gly Asp Thr Glu Asp Glu Asp Ser Ala 1810 1815 1820 Ser Thr Ser Ser Ser Leu Lys Arg Gly Asn Lys Asp Leu Gln Lys Arg 1825 1830 1835 1840 Lys Met Glu Glu Asn Thr Ser Ile Asn Leu Ser Lys Gln Glu Ser Phe 1845 1850 1855 Thr Ser Val Lys Lys Pro Lys Arg Asp Asp Ser Lys Asp Leu Ala Leu 1860 1865 1870 Cys Ser Met Ile Leu Thr Glu Met Glu Thr His Glu Asp Ala Trp Pro 1875 1880 1885 Phe Leu Leu Pro Val Asn Leu Lys Leu Val Pro Gly Tyr Lys Lys Val 1890 1895 1900 Ile Lys Lys Pro Met Asp Phe Ser Thr Ile Arg Glu Lys Leu Ser Ser 1905 1910 1915 1920 Gly Gln Tyr Pro Asn Leu Glu Thr Phe Ala Leu Asp Val Arg Leu Val 1925 1930 1935 Phe Asp Asn Cys Glu Thr Phe Asn Glu Asp Asp Ser Asp Ile Gly Arg 1940 1945 1950 Ala Gly His Asn Met Arg Lys Tyr Phe Glu Lys Lys Trp Thr Asp Thr 1955 1960 1965 Phe Lys Val Ser 1970 22 7585 DNA Homo sapiens CDS (367)...(6282) 22 ggtctcgatc tcctgacctt gtgatccacc tcctcggcct cccaaagtgc tgggattaca 60 ggcatgagcc acggcaccca gcctcatttg ctgttaaact catttattga gtcacctttt 120 tcttcctcac actttttagt cttagaattt ttgtgtgttt ttatttaccc taacctgtca 180 atttcatagt ttccactttc ttgttgaagt ttccaaactt gacctcatgc ctttgaatat 240 actaattcta ttgctttgac acattttttt cccgaaaaag gtgtaaatgg gtcaataaat 300 ggaagtaata catcatctgt aattggtatc aacacatctg tactatccac tactgcttca 360 agttcc atg gga caa act aaa agt aca agc tca ggt gga gga aat cga 408 Met Gly Gln Thr Lys Ser Thr Ser Ser Gly Gly Gly Asn Arg 1 5 10 aaa tgt aat cag gaa caa agc aaa aac cag cct ttg gat gct aga gtt 456 Lys Cys Asn Gln Glu Gln Ser Lys Asn Gln Pro Leu Asp Ala Arg Val 15 20 25 30 gac aaa atc aaa gat aag aaa cca agg aag aaa gca atg gaa agt tct 504 Asp Lys Ile Lys Asp Lys Lys Pro Arg Lys Lys Ala Met Glu Ser Ser 35 40 45 agc aac agt gat agt gat tca ggc aca tca tca gac acc tca agt gaa 552 Ser Asn Ser Asp Ser Asp Ser Gly Thr Ser Ser Asp Thr Ser Ser Glu 50 55 60 ggc att agt agc agt gat tca gat gat cta gaa gaa gat gaa gaa gaa 600 Gly Ile Ser Ser Ser Asp Ser Asp Asp Leu Glu Glu Asp Glu Glu Glu 65 70 75 gaa gat caa agt att gaa gaa agt gaa gat gat gat tct gat tca gag 648 Glu Asp Gln Ser Ile Glu Glu Ser Glu Asp Asp Asp Ser Asp Ser Glu 80 85 90 agt gaa gca caa cat aaa agt aac aac cag gtg cta tta cat ggt att 696 Ser Glu Ala Gln His Lys Ser Asn Asn Gln Val Leu Leu His Gly Ile 95 100 105 110 tca gac cca aaa gca gat gga cag aaa gca act gaa aaa gcc cag gaa 744 Ser Asp Pro Lys Ala Asp Gly Gln Lys Ala Thr Glu Lys Ala Gln Glu 115 120 125 aaa aga ata cac cag cca tta cct ctt gcg ttt gaa tcc cag act cac 792 Lys Arg Ile His Gln Pro Leu Pro Leu Ala Phe Glu Ser Gln Thr His 130 135 140 tca ttc caa tcc cag cag aag cag cct cag gtt ttg tca cag cag ctt 840 Ser Phe Gln Ser Gln Gln Lys Gln Pro Gln Val Leu Ser Gln Gln Leu 145 150 155 cca ttt att ttc caa agc tct cag gca aag gag gaa tct gtg aac aaa 888 Pro Phe Ile Phe Gln Ser Ser Gln Ala Lys Glu Glu Ser Val Asn Lys 160 165 170 cac acc agt gta ata cag tct acg gga ttg gtg tcc aat gtg aaa cct 936 His Thr Ser Val Ile Gln Ser Thr Gly Leu Val Ser Asn Val Lys Pro 175 180 185 190 tta tct ttg gta aat caa gcc aaa aag gaa act tac atg aaa ctc ata 984 Leu Ser Leu Val Asn Gln Ala Lys Lys Glu Thr Tyr Met Lys Leu Ile 195 200 205 gtt cct tct cct gat gtt ctt aaa gca ggg aat aaa aat acc tct gaa 1032 Val Pro Ser Pro Asp Val Leu Lys Ala Gly Asn Lys Asn Thr Ser Glu 210 215 220 gaa tct agt tta ttg acc agt gaa ttg aga tcc aaa cgg gaa caa tat 1080 Glu Ser Ser Leu Leu Thr Ser Glu Leu Arg Ser Lys Arg Glu Gln Tyr 225 230 235 aaa cag gca ttc cca tca cag tta aag aaa caa gag tca tcg aag agc 1128 Lys Gln Ala Phe Pro Ser Gln Leu Lys Lys Gln Glu Ser Ser Lys Ser 240 245 250 ctg aag aag gtt att gca gct ttg tca aat cca aaa gca acc tct agt 1176 Leu Lys Lys Val Ile Ala Ala Leu Ser Asn Pro Lys Ala Thr Ser Ser 255 260 265 270 tca cca gca cat cca aaa caa aca tta gaa aac aac cac cca aat cca 1224 Ser Pro Ala His Pro Lys Gln Thr Leu Glu Asn Asn His Pro Asn Pro 275 280 285 ttc ttg aca aat gca ctt tta ggt aat cac caa cca aat gga gtt att 1272 Phe Leu Thr Asn Ala Leu Leu Gly Asn His Gln Pro Asn Gly Val Ile 290 295 300 caa agt gtc att caa gaa gct cct cta gca ctt act acc aaa act aaa 1320 Gln Ser Val Ile Gln Glu Ala Pro Leu Ala Leu Thr Thr Lys Thr Lys 305 310 315 atg cag agc aag att aat gaa aac att gct gct gca agt agc acc cct 1368 Met Gln Ser Lys Ile Asn Glu Asn Ile Ala Ala Ala Ser Ser Thr Pro 320 325 330 ttt tcc tca cct gta aat ctg agt aca agt ggg aga aga acc cct ggc 1416 Phe Ser Ser Pro Val Asn Leu Ser Thr Ser Gly Arg Arg Thr Pro Gly 335 340 345 350 aat cag aca cct gta atg cct tct gcc tct ccc atc ctg cat agt caa 1464 Asn Gln Thr Pro Val Met Pro Ser Ala Ser Pro Ile Leu His Ser Gln 355 360 365 ggg aag gaa aaa gca gtt agc aat aat gta aac cca gta aaa aca cag 1512 Gly Lys Glu Lys Ala Val Ser Asn Asn Val Asn Pro Val Lys Thr Gln 370 375 380 cat cac tcc cat cct gca aaa tct tta gtg gaa caa ttc aga gga aca 1560 His His Ser His Pro Ala Lys Ser Leu Val Glu Gln Phe Arg Gly Thr 385 390 395 gat tca gac att ccc agt agt aaa gat tct gaa gat tca aat gag gat 1608 Asp Ser Asp Ile Pro Ser Ser Lys Asp Ser Glu Asp Ser Asn Glu Asp 400 405 410 gaa gag gaa gat gat gaa gaa gaa gat gag gaa gat gat gaa gat gat 1656 Glu Glu Glu Asp Asp Glu Glu Glu Asp Glu Glu Asp Asp Glu Asp Asp 415 420 425 430 gaa tct gat gac agc caa tca gaa tca gat agt aat tca gaa tca gat 1704 Glu Ser Asp Asp Ser Gln Ser Glu Ser Asp Ser Asn Ser Glu Ser Asp 435 440 445 aca gaa gga tca gaa gaa gaa gat gat gat gat aaa gac caa gat gaa 1752 Thr Glu Gly Ser Glu Glu Glu Asp Asp Asp Asp Lys Asp Gln Asp Glu 450 455 460 tca gat agt gat act gaa gga gag aaa act tca atg aaa ctg aat aaa 1800 Ser Asp Ser Asp Thr Glu Gly Glu Lys Thr Ser Met Lys Leu Asn Lys 465 470 475 aca act tcc tct gtc aaa agc cct tcc atg agt ctc aca ggt cac tca 1848 Thr Thr Ser Ser Val Lys Ser Pro Ser Met Ser Leu Thr Gly His Ser 480 485 490 aca cct cgt aac ctc cac ata gca aaa gcc cca ggc tct gct cct gct 1896 Thr Pro Arg Asn Leu His Ile Ala Lys Ala Pro Gly Ser Ala Pro Ala 495 500 505 510 gcc tta tgt tct gaa tcc cag tca cct gct ttt ctt ggt aca tct tct 1944 Ala Leu Cys Ser Glu Ser Gln Ser Pro Ala Phe Leu Gly Thr Ser Ser 515 520 525 tcc aca ctt act tca agc cca cac tct ggc act tcc aaa aga aga aga 1992 Ser Thr Leu Thr Ser Ser Pro His Ser Gly Thr Ser Lys Arg Arg Arg 530 535 540 gta aca gat gaa cgt gaa ctg cgt att cca ttg gaa tat ggc tgg cag 2040 Val Thr Asp Glu Arg Glu Leu Arg Ile Pro Leu Glu Tyr Gly Trp Gln 545 550 555 aga gag aca aga ata aga aac ttt gga ggg cgc ctt caa gga gaa gta 2088 Arg Glu Thr Arg Ile Arg Asn Phe Gly Gly Arg Leu Gln Gly Glu Val 560 565 570 gca tat tat gct cca tgt gga aag aaa ctt agg cag tac cct gaa gta 2136 Ala Tyr Tyr Ala Pro Cys Gly Lys Lys Leu Arg Gln Tyr Pro Glu Val 575 580 585 590 ata aag tat ctc agc aga aat gga ata atg gat atc tca agg gac aat 2184 Ile Lys Tyr Leu Ser Arg Asn Gly Ile Met Asp Ile Ser Arg Asp Asn 595 600 605 ttc agc ttc agt gca aaa ata aga gtg ggt gac ttc tat gaa gcc aga 2232 Phe Ser Phe Ser Ala Lys Ile Arg Val Gly Asp Phe Tyr Glu Ala Arg 610 615 620 gat gga ccg cag gaa atg cag tgg tgt ctt ttg aaa gaa gag gat gtc 2280 Asp Gly Pro Gln Glu Met Gln Trp Cys Leu Leu Lys Glu Glu Asp Val 625 630 635 att cct cgt atc agg gca atg gaa ggt cgt aga gga aga cca cca aat 2328 Ile Pro Arg Ile Arg Ala Met Glu Gly Arg Arg Gly Arg Pro Pro Asn 640 645 650 cca gat aga caa cga gca aga gag gaa tcc agg atg aga cgt cgg aaa 2376 Pro Asp Arg Gln Arg Ala Arg Glu Glu Ser Arg Met Arg Arg Arg Lys 655 660 665 670 ggt cga cct cca aat gtt ggc aat gct gaa ttc cta gat aac gca gat 2424 Gly Arg Pro Pro Asn Val Gly Asn Ala Glu Phe Leu Asp Asn Ala Asp 675 680 685 gca aag ttg cta aga aaa ctg caa gct caa gaa ata gcc agg caa gca 2472 Ala Lys Leu Leu Arg Lys Leu Gln Ala Gln Glu Ile Ala Arg Gln Ala 690 695 700 gca caa ata aag ctt ttg aga aaa ctt caa aag cag gaa cag gct cgg 2520 Ala Gln Ile Lys Leu Leu Arg Lys Leu Gln Lys Gln Glu Gln Ala Arg 705 710 715 gtt gct aaa gaa gcc aaa aaa caa caa gca ata atg gct gct gag gag 2568 Val Ala Lys Glu Ala Lys Lys Gln Gln Ala Ile Met Ala Ala Glu Glu 720 725 730 aag cgg aag caa aaa gaa cag ata aag att atg aaa cag cag gaa aaa 2616 Lys Arg Lys Gln Lys Glu Gln Ile Lys Ile Met Lys Gln Gln Glu Lys 735 740 745 750 att aag aga ata cag caa atc aga atg gaa aaa gaa ctt cga gct cag 2664 Ile Lys Arg Ile Gln Gln Ile Arg Met Glu Lys Glu Leu Arg Ala Gln 755 760 765 caa att cta gag gct aaa aag aaa aag aag gaa gaa gcg gca aat gcc 2712 Gln Ile Leu Glu Ala Lys Lys Lys Lys Lys Glu Glu Ala Ala Asn Ala 770 775 780 aaa tta ttg gag gcc gag aaa cga ata aag gaa aaa gaa atg aga aga 2760 Lys Leu Leu Glu Ala Glu Lys Arg Ile Lys Glu Lys Glu Met Arg Arg 785 790 795 caa caa gct gtt ctt ctg aaa cat cag gaa cga gag cga agg cga caa 2808 Gln Gln Ala Val Leu Leu Lys His Gln Glu Arg Glu Arg Arg Arg Gln 800 805 810 cac atg atg ctt atg aaa gct atg gaa gct cgt aaa aaa gca gaa gaa 2856 His Met Met Leu Met Lys Ala Met Glu Ala Arg Lys Lys Ala Glu Glu 815 820 825 830 aaa gag cgg ttg aaa caa gaa aaa cgt gat gag aaa aga tta aat aaa 2904 Lys Glu Arg Leu Lys Gln Glu Lys Arg Asp Glu Lys Arg Leu Asn Lys 835 840 845 gag cgt aaa cta gag cag cga aga tta gaa tta gaa atg gca aag gaa 2952 Glu Arg Lys Leu Glu Gln Arg Arg Leu Glu Leu Glu Met Ala Lys Glu 850 855 860 cta aag aag cct aat gaa gac atg tgc tta gca gac caa aag cct ttg 3000 Leu Lys Lys Pro Asn Glu Asp Met Cys Leu Ala Asp Gln Lys Pro Leu 865 870 875 cca gag ttg cct cgt att cca gga ctt gtt ctc tct gga agt aca ttt 3048 Pro Glu Leu Pro Arg Ile Pro Gly Leu Val Leu Ser Gly Ser Thr Phe 880 885 890 tca gac tgt ctc atg gtg gtg cag ttc tta cga aac ttt ggt aaa gtt 3096 Ser Asp Cys Leu Met Val Val Gln Phe Leu Arg Asn Phe Gly Lys Val 895 900 905 910 ttg ggc ttt gat gtg aat att gat gtt cca aac ctg agt gtt ctt caa 3144 Leu Gly Phe Asp Val Asn Ile Asp Val Pro Asn Leu Ser Val Leu Gln 915 920 925 gag gga ttg cta aat ata ggg gac agc atg ggt gaa gta caa gac ttg 3192 Glu Gly Leu Leu Asn Ile Gly Asp Ser Met Gly Glu Val Gln Asp Leu 930 935 940 ctt gtg agg ctc ctc tca gct gct gta tgt gat cca ggt cta ata aca 3240 Leu Val Arg Leu Leu Ser Ala Ala Val Cys Asp Pro Gly Leu Ile Thr 945 950 955 gga tac aag gct aaa aca gct ctt gga gaa cat ttg ctg aat gtt ggt 3288 Gly Tyr Lys Ala Lys Thr Ala Leu Gly Glu His Leu Leu Asn Val Gly 960 965 970 gtg aat cga gac aat gtt tcc gag att tta cag ata ttt atg gaa gcc 3336 Val Asn Arg Asp Asn Val Ser Glu Ile Leu Gln Ile Phe Met Glu Ala 975 980 985 990 cac tgt gga caa act gag ctt act gaa agt ctg aag acc aaa gct ttt 3384 His Cys Gly Gln Thr Glu Leu Thr Glu Ser Leu Lys Thr Lys Ala Phe 995 1000 1005 cag gct cac act cca gca cag aaa gct tca gtc ctg gct ttc ctg atc 3432 Gln Ala His Thr Pro Ala Gln Lys Ala Ser Val Leu Ala Phe Leu Ile 1010 1015 1020 aat gaa ctg gca tgc agc aag agt gtg gtc agt gaa atc gac aag aac 3480 Asn Glu Leu Ala Cys Ser Lys Ser Val Val Ser Glu Ile Asp Lys Asn 1025 1030 1035 att gat tat atg tca aac ttg agg aga gat aaa tgg gtg gta gaa ggt 3528 Ile Asp Tyr Met Ser Asn Leu Arg Arg Asp Lys Trp Val Val Glu Gly 1040 1045 1050 aaa ctc cgc aag ctc aga atc att cat gct aag aaa aca ggc aaa aga 3576 Lys Leu Arg Lys Leu Arg Ile Ile His Ala Lys Lys Thr Gly Lys Arg 1055 1060 1065 1070 gac act tca ggt ggc att gat ctg gga gaa gag cag cat ccc ttg ggc 3624 Asp Thr Ser Gly Gly Ile Asp Leu Gly Glu Glu Gln His Pro Leu Gly 1075 1080 1085 aca ccc act cca gga cgc aag cga aga agg aag gga gga gac agt gat 3672 Thr Pro Thr Pro Gly Arg Lys Arg Arg Arg Lys Gly Gly Asp Ser Asp 1090 1095 1100 tat gac gat gat gat gac gat gac agt gat gac caa ggg gat gaa gat 3720 Tyr Asp Asp Asp Asp Asp Asp Asp Ser Asp Asp Gln Gly Asp Glu Asp 1105 1110 1115 gat gag gat gaa gaa gat aag gaa gac caa aaa gga aaa aag act gat 3768 Asp Glu Asp Glu Glu Asp Lys Glu Asp Gln Lys Gly Lys Lys Thr Asp 1120 1125 1130 atc tgt gaa gat gag gat gaa ggt gac caa gca gca agt gtt gaa gag 3816 Ile Cys Glu Asp Glu Asp Glu Gly Asp Gln Ala Ala Ser Val Glu Glu 1135 1140 1145 1150 ctg gaa aaa cag att gaa aaa ctg agt aaa caa cag agt cag tac aga 3864 Leu Glu Lys Gln Ile Glu Lys Leu Ser Lys Gln Gln Ser Gln Tyr Arg 1155 1160 1165 agg aag ctc ttt gat gcg tct cac tca ttg cgt tca gtg atg ttt ggc 3912 Arg Lys Leu Phe Asp Ala Ser His Ser Leu Arg Ser Val Met Phe Gly 1170 1175 1180 cca gat cgt tac aga cgc cgg tac tgg att ctt ccc cga tgt ggg ggg 3960 Pro Asp Arg Tyr Arg Arg Arg Tyr Trp Ile Leu Pro Arg Cys Gly Gly 1185 1190 1195 att ttt gta gaa ggc atg gag agt ggt gaa gga cta gaa gaa att gca 4008 Ile Phe Val Glu Gly Met Glu Ser Gly Glu Gly Leu Glu Glu Ile Ala 1200 1205 1210 aaa gaa aga gaa aaa ctg aaa aag gca gaa agt gtc cag atc aaa gaa 4056 Lys Glu Arg Glu Lys Leu Lys Lys Ala Glu Ser Val Gln Ile Lys Glu 1215 1220 1225 1230 gaa atg ttt gag act tct ggg gac agt tta aat tgt tca aat aca gat 4104 Glu Met Phe Glu Thr Ser Gly Asp Ser Leu Asn Cys Ser Asn Thr Asp 1235 1240 1245 cac tgt gaa caa aag gaa gat ctt aaa gaa aaa gat aac aca aat cta 4152 His Cys Glu Gln Lys Glu Asp Leu Lys Glu Lys Asp Asn Thr Asn Leu 1250 1255 1260 ttc ctt cag aaa cct ggc tct ttt tcc aaa tta agc aag ctt ttg gaa 4200 Phe Leu Gln Lys Pro Gly Ser Phe Ser Lys Leu Ser Lys Leu Leu Glu 1265 1270 1275 gta gct aag atg cct cct gag tca gag gtt atg acc ccc aaa cca aat 4248 Val Ala Lys Met Pro Pro Glu Ser Glu Val Met Thr Pro Lys Pro Asn 1280 1285 1290 gct ggt gca aat ggg tgc acg ttg tct tat cag aac agt gga aaa cat 4296 Ala Gly Ala Asn Gly Cys Thr Leu Ser Tyr Gln Asn Ser Gly Lys His 1295 1300 1305 1310 tca ctg ggc agc gtt cag tca aca gca acg caa agc aat gtg gaa aag 4344 Ser Leu Gly Ser Val Gln Ser Thr Ala Thr Gln Ser Asn Val Glu Lys 1315 1320 1325 gca gac tct aat aat ctg ttt aat act ggt tca agt ggt cca ggg aag 4392 Ala Asp Ser Asn Asn Leu Phe Asn Thr Gly Ser Ser Gly Pro Gly Lys 1330 1335 1340 ttc tac agt cct ctc ccc aat gac cag tta cta aaa acg ctg act gaa 4440 Phe Tyr Ser Pro Leu Pro Asn Asp Gln Leu Leu Lys Thr Leu Thr Glu 1345 1350 1355 aag aat aga caa tgg ttt agt ctt ttg cca cga aca ccc tgt gat gac 4488 Lys Asn Arg Gln Trp Phe Ser Leu Leu Pro Arg Thr Pro Cys Asp Asp 1360 1365 1370 act tca ctt act cat gcc gat atg tca act gct tct ttg gtg act cct 4536 Thr Ser Leu Thr His Ala Asp Met Ser Thr Ala Ser Leu Val Thr Pro 1375 1380 1385 1390 cag tct cag cca cca tct aag tca cct tca cct acc cca gct cct ctt 4584 Gln Ser Gln Pro Pro Ser Lys Ser Pro Ser Pro Thr Pro Ala Pro Leu 1395 1400 1405 gga tct tct gct cag aat cct gtt ggc tta aat cca ttt gct tta tca 4632 Gly Ser Ser Ala Gln Asn Pro Val Gly Leu Asn Pro Phe Ala Leu Ser 1410 1415 1420 cct ctt cag gtg aaa ggt gga gta tct atg atg gga ctt cag ttt tgt 4680 Pro Leu Gln Val Lys Gly Gly Val Ser Met Met Gly Leu Gln Phe Cys 1425 1430 1435 gga tgg ccc act ggt gtg gtt act tct aat att cca ttt aca tta tct 4728 Gly Trp Pro Thr Gly Val Val Thr Ser Asn Ile Pro Phe Thr Leu Ser 1440 1445 1450 gta cct agt cta gga tcg ggg tta ggg tta tca gaa gga aat ggt aat 4776 Val Pro Ser Leu Gly Ser Gly Leu Gly Leu Ser Glu Gly Asn Gly Asn 1455 1460 1465 1470 tca ttc ttg act tcc aat gtt gct tca agt aaa agt gaa tct cca gta 4824 Ser Phe Leu Thr Ser Asn Val Ala Ser Ser Lys Ser Glu Ser Pro Val 1475 1480 1485 cca cag aat gaa aag gcc act tca gct caa cct gca gct gtt gaa gta 4872 Pro Gln Asn Glu Lys Ala Thr Ser Ala Gln Pro Ala Ala Val Glu Val 1490 1495 1500 gca aaa cca gta gat ttt cct agt cca aaa cct att cca gaa gaa atg 4920 Ala Lys Pro Val Asp Phe Pro Ser Pro Lys Pro Ile Pro Glu Glu Met 1505 1510 1515 cag ttt ggt tgg tgg aga att att gac cca gag gac cta aaa gct ttg 4968 Gln Phe Gly Trp Trp Arg Ile Ile Asp Pro Glu Asp Leu Lys Ala Leu 1520 1525 1530 ctc aaa gtg ctg cat ctc aga gga ata aga gaa aag gca tta caa aaa 5016 Leu Lys Val Leu His Leu Arg Gly Ile Arg Glu Lys Ala Leu Gln Lys 1535 1540 1545 1550 caa att cag aaa cat ttg gat tat att act caa gcc tgc ctc aag aat 5064 Gln Ile Gln Lys His Leu Asp Tyr Ile Thr Gln Ala Cys Leu Lys Asn 1555 1560 1565 aag gat gtt gct att att gaa ctg aat gaa aat gaa gaa aac caa gta 5112 Lys Asp Val Ala Ile Ile Glu Leu Asn Glu Asn Glu Glu Asn Gln Val 1570 1575 1580 act cga gat att gtg gag aac tgg tca gta gaa gaa caa gca atg gaa 5160 Thr Arg Asp Ile Val Glu Asn Trp Ser Val Glu Glu Gln Ala Met Glu 1585 1590 1595 atg gat ttg agt gtc ctt caa cag gta gaa gat cta gaa agg aga gtt 5208 Met Asp Leu Ser Val Leu Gln Gln Val Glu Asp Leu Glu Arg Arg Val 1600 1605 1610 gca tcc gca agt ttg caa gtg aag ggt tgg atg tgt cca gag cct gca 5256 Ala Ser Ala Ser Leu Gln Val Lys Gly Trp Met Cys Pro Glu Pro Ala 1615 1620 1625 1630 tca gaa agg gag gac ttg gta tat ttt gaa cat aaa tca ttt act aaa 5304 Ser Glu Arg Glu Asp Leu Val Tyr Phe Glu His Lys Ser Phe Thr Lys 1635 1640 1645 ttg tgc aag gag cat gat gga gaa ttt act ggc gaa gac gaa agc agt 5352 Leu Cys Lys Glu His Asp Gly Glu Phe Thr Gly Glu Asp Glu Ser Ser 1650 1655 1660 gca cat gca cta gaa cgg aag agt gac aac ccc cta gat ata gct gtt 5400 Ala His Ala Leu Glu Arg Lys Ser Asp Asn Pro Leu Asp Ile Ala Val 1665 1670 1675 acc agg ctg gct gat ttg gag cgg aac att gaa aga aga att gag gaa 5448 Thr Arg Leu Ala Asp Leu Glu Arg Asn Ile Glu Arg Arg Ile Glu Glu 1680 1685 1690 gat att gct cca ggg ctc agg gtg tgg aga agg gca tta tca gaa gct 5496 Asp Ile Ala Pro Gly Leu Arg Val Trp Arg Arg Ala Leu Ser Glu Ala 1695 1700 1705 1710 cgc agt gct gca cag gta gct ctg tgc att cag caa tta cag aaa tca 5544 Arg Ser Ala Ala Gln Val Ala Leu Cys Ile Gln Gln Leu Gln Lys Ser 1715 1720 1725 ata gca tgg gaa aaa tca att atg aaa gtt tac tgc caa atc tgt cga 5592 Ile Ala Trp Glu Lys Ser Ile Met Lys Val Tyr Cys Gln Ile Cys Arg 1730 1735 1740 aag gga gat aat gaa gaa ctg ctt ctt ctt tgt gat ggc tgt gac aaa 5640 Lys Gly Asp Asn Glu Glu Leu Leu Leu Leu Cys Asp Gly Cys Asp Lys 1745 1750 1755 ggc tgt cat acc tac tgc cat aga ccc aag att aca aca atc cca gat 5688 Gly Cys His Thr Tyr Cys His Arg Pro Lys Ile Thr Thr Ile Pro Asp 1760 1765 1770 gga gac tgg ttt tgt cca gct tgc att gct aag gca agt ggt caa act 5736 Gly Asp Trp Phe Cys Pro Ala Cys Ile Ala Lys Ala Ser Gly Gln Thr 1775 1780 1785 1790 cta aaa atc aaa aaa ctt cat gtc aaa gga aaa aag act aat gag tct 5784 Leu Lys Ile Lys Lys Leu His Val Lys Gly Lys Lys Thr Asn Glu Ser 1795 1800 1805 aag aaa ggc aag aag gta act tta aca gga gat act gaa gat gaa gac 5832 Lys Lys Gly Lys Lys Val Thr Leu Thr Gly Asp Thr Glu Asp Glu Asp 1810 1815 1820 tct gca tct aca agt agt tca cta aaa aga gga aac aaa gac ctc cag 5880 Ser Ala Ser Thr Ser Ser Ser Leu Lys Arg Gly Asn Lys Asp Leu Gln 1825 1830 1835 aaa aga aaa atg gag gaa aac act tct att aac ttg tca aaa caa gaa 5928 Lys Arg Lys Met Glu Glu Asn Thr Ser Ile Asn Leu Ser Lys Gln Glu 1840 1845 1850 agt ttt act tca gtt aag aaa cct aaa aga gat gac tcc aag gac cta 5976 Ser Phe Thr Ser Val Lys Lys Pro Lys Arg Asp Asp Ser Lys Asp Leu 1855 1860 1865 1870 gct ctt tgc agt atg att ctg act gaa atg gaa act cat gag gat gca 6024 Ala Leu Cys Ser Met Ile Leu Thr Glu Met Glu Thr His Glu Asp Ala 1875 1880 1885 tgg cct ttt cta ctt cct gta aac ttg aaa ctt gtt cct ggt tat aag 6072 Trp Pro Phe Leu Leu Pro Val Asn Leu Lys Leu Val Pro Gly Tyr Lys 1890 1895 1900 aaa gtt att aag aag cct atg gat ttt tcc aca att aga gag aaa cta 6120 Lys Val Ile Lys Lys Pro Met Asp Phe Ser Thr Ile Arg Glu Lys Leu 1905 1910 1915 agt agt gga cag tat cca aac ctt gaa acc ttt gct cta gat gtc agg 6168 Ser Ser Gly Gln Tyr Pro Asn Leu Glu Thr Phe Ala Leu Asp Val Arg 1920 1925 1930 ctt gtt ttt gac aac tgt gaa aca ttt aat gaa gat gat tct gat ata 6216 Leu Val Phe Asp Asn Cys Glu Thr Phe Asn Glu Asp Asp Ser Asp Ile 1935 1940 1945 1950 ggc aga gct ggc cac aat atg agg aag tat ttt gaa aaa aag tgg aca 6264 Gly Arg Ala Gly His Asn Met Arg Lys Tyr Phe Glu Lys Lys Trp Thr 1955 1960 1965 gat act ttc aaa gtg agc tgaagttata ataatctctt tatttttttc 6312 Asp Thr Phe Lys Val Ser 1970 cttctaaaca aggacaaatg agaccagcaa tgtgaactgt atttacataa acgtgcaagg 6372 cacatacata atgactttct ttttccttaa gtataaaaaa aaagtatcag aagaatgata 6432 ccatttttaa aggcttcatt cctacaacaa ccaaggccct cggttattgg tttgtgtgat 6492 ttatcagcta atttaggtag aacagggaag cacacccaaa gaattttcaa aggaaagggt 6552 gttatagtgc aatagcaatt aaaatatatc aaatcgcact gaatactcaa caccagagct 6612 ctaatgtggg aaatggttct cctttccctc tcaataaata tctatttttc atttttttac 6672 tttgtagttt attttttagt gaatgtattt aattttatga attatttatg attaaaccac 6732 atccagaatc ttcgttttct gtgaaaagga agaactagaa aattgcttta aatcttgaaa 6792 atacaaggaa tgttttaaaa tataaaacaa agccaagtta aactgtttac actgatgtgc 6852 tataaaagca ccaaaaagaa actttactgt agagttacaa gtacatttat atatatatgt 6912 tgctgcatca cttgtgtagt taaattgtat ttcaaaacag tgaaaaaatt gacatgtata 6972 tactgttcat tcttgtttat attaagtctt gttttaaata tgtattatgt gtatatattg 7032 tttgcagaca ttattgttca tgccttagag gattgtagca ttttattttc gtctgaaggt 7092 aatgatagct atacagtctg tacagtaatt atcctctacc aacactgtgg cgtctcctta 7152 atcttggtag tgcctgcctt tgaaacaggg tgtaggggat attagttttc catttttcta 7212 ttttgttata taattttaag ccaccagggc ctaaattaaa gtataatcat ttgtatccat 7272 gtggaataaa attgtgacaa tttcctacgc acacagtatt ttttcataga aacatttccc 7332 tcccatttgc cttgcctcag aaataaattt aaaagacgtt tgtaaccact gtgttttatc 7392 tactgtgtgt tgtggtggcc tgttggaggc aaatagatca gatttttttt gtacctacgt 7452 aagagtactt gaagttttat ttaaaataaa atgttgtgga aaaggtagca ttcttttttt 7512 aggagtgtta tttttcacta tgtgtggcac ggatacaata aaagactttt acaaactaaa 7572 aaaaaaaaaa aaa 7585 23 25 DNA Artificial Sequence Synthetically generated primer 23 ctgactgaaa tggaaactca tgagg 25 24 25 DNA Artificial Sequence Synthetically generated primer 24 ctagagcaaa ggtttcaagg tttgg 25 25 24 DNA Artificial Sequence Synthetically generated primer 25 tgttgctgca tcacttgtgt agtt 24 26 23 DNA Artificial Sequence Synthetically generated primer 26 ggcatgacaa taatgtctgc aaa 23 27 1527 PRT Homo sapiens 27 Met Ala Pro Leu Leu Gly Arg Lys Pro Phe Pro Leu Val Asn Pro Leu 1 5 10 15 Pro Gly Glu Glu Pro Phe Phe Thr Ile Pro His Thr Gln Glu Ala Phe 20 25 30 Arg Thr Arg Glu Glu Tyr Glu Ala Arg Leu Glu Arg Tyr Ser Glu Arg 35 40 45 Ile Trp Thr Cys Lys Ser Thr Gly Ser Ser Gln Leu Thr His Lys Glu 50 55 60 Ala Trp Glu Glu Glu Gln Glu Val Ala Glu Leu Leu Lys Glu Glu Phe 65 70 75 80 Pro Ala Trp Tyr Glu Lys Leu Val Leu Glu Met Val His His Asn Thr 85 90 95 Ala Ser Leu Glu Lys Leu Val Asp Thr Ala Trp Leu Glu Ile Met Thr 100 105 110 Lys Tyr Ala Val Gly Glu Glu Cys Asp Phe Glu Val Gly Lys Glu Lys 115 120 125 Met Leu Lys Val Lys Ile Val Lys Ile His Pro Leu Glu Lys Val Asp 130 135 140 Glu Glu Ala Thr Glu Lys Lys Ser Asp Gly Ala Cys Asp Ser Pro Ser 145 150 155 160 Ser Asp Lys Glu Asn Ser Ser Gln Ile Ala Gln Asp His Gln Lys Lys 165 170 175 Glu Thr Val Val Lys Glu Asp Glu Gly Arg Arg Glu Ser Ile Asn Asp 180 185 190 Arg Ala Arg Arg Ser Pro Arg Lys Leu Pro Thr Ser Leu Lys Lys Gly 195 200 205 Glu Arg Lys Trp Ala Pro Pro Lys Phe Leu Pro His Lys Tyr Asp Val 210 215 220 Lys Leu Gln Asn Glu Asp Lys Ile Ile Ser Asn Val Pro Ala Asp Ser 225 230 235 240 Leu Ile Arg Thr Glu Arg Pro Pro Asn Lys Glu Ile Val Arg Tyr Phe 245 250 255 Ile Arg His Asn Ala Leu Arg Ala Gly Thr Gly Glu Asn Ala Pro Trp 260 265 270 Val Val Glu Asp Glu Leu Val Lys Lys Tyr Ser Leu Pro Ser Lys Phe 275 280 285 Ser Asp Phe Leu Leu Asp Pro Tyr Lys Tyr Met Thr Leu Asn Pro Ser 290 295 300 Thr Lys Arg Lys Asn Thr Gly Ser Pro Asp Arg Lys Pro Ser Lys Lys 305 310 315 320 Ser Lys Thr Asp Asn Ser Ser Leu Ser Ser Pro Leu Asn Pro Lys Leu 325 330 335 Trp Cys His Val His Leu Lys Lys Ser Leu Ser Gly Ser Pro Leu Lys 340 345 350 Val Lys Asn Ser Lys Asn Ser Lys Ser Pro Glu Glu His Leu Glu Glu 355 360 365 Met Met Lys Met Met Ser Pro Asn Lys Leu His Thr Asn Phe His Ile 370 375 380 Pro Lys Lys Gly Pro Pro Ala Lys Lys Pro Gly Lys His Ser Asp Lys 385 390 395 400 Pro Leu Lys Ala Lys Gly Arg Ser Lys Gly Ile Leu Asn Gly Gln Lys 405 410 415 Ser Thr Gly Asn Ser Lys Ser Pro Lys Lys Gly Leu Lys Thr Pro Lys 420 425 430 Thr Lys Met Lys Gln Met Thr Leu Leu Asp Met Ala Lys Gly Thr Gln 435 440 445 Lys Met Thr Arg Ala Pro Arg Asn Ser Gly Gly Thr Pro Arg Thr Ser 450 455 460 Ser Lys Pro His Lys His Leu Pro Pro Ala Ala Leu His Leu Ile Ala 465 470 475 480 Tyr Tyr Lys Glu Asn Lys Asp Arg Glu Asp Lys Arg Ser Ala Leu Ser 485 490 495 Cys Val Ile Ser Lys Thr Ala Arg Leu Leu Ser Ser Glu Asp Arg Ala 500 505 510 Arg Leu Pro Glu Glu Leu Arg Ser Leu Val Gln Lys Arg Tyr Glu Leu 515 520 525 Leu Glu His Lys Lys Arg Trp Ala Ser Met Ser Glu Glu Gln Arg Lys 530 535 540 Glu Tyr Leu Lys Lys Lys Arg Glu Glu Leu Lys Lys Lys Leu Lys Glu 545 550 555 560 Lys Ala Lys Glu Arg Arg Glu Lys Glu Met Leu Glu Arg Leu Glu Lys 565 570 575 Gln Lys Arg Tyr Glu Asp Gln Glu Leu Thr Gly Lys Asn Leu Pro Ala 580 585 590 Phe Arg Leu Val Asp Thr Pro Glu Gly Leu Pro Asn Thr Leu Phe Gly 595 600 605 Asp Val Ala Met Val Val Glu Phe Leu Ser Cys Tyr Ser Gly Leu Leu 610 615 620 Leu Pro Asp Ala Gln Tyr Pro Ile Thr Ala Val Ser Leu Met Glu Ala 625 630 635 640 Leu Ser Ala Asp Lys Gly Gly Phe Leu Tyr Leu Asn Arg Val Leu Val 645 650 655 Ile Leu Leu Gln Thr Leu Leu Gln Asp Glu Ile Ala Glu Asp Tyr Gly 660 665 670 Glu Leu Gly Met Lys Leu Ser Glu Ile Pro Leu Thr Leu His Ser Val 675 680 685 Ser Glu Leu Val Arg Leu Cys Leu Arg Arg Ser Asp Val Gln Glu Glu 690 695 700 Ser Glu Gly Ser Asp Thr Asp Asp Asn Lys Asp Ser Ala Ala Phe Glu 705 710 715 720 Asp Asn Glu Val Gln Asp Glu Phe Leu Glu Lys Leu Glu Thr Ser Glu 725 730 735 Phe Phe Glu Leu Thr Ser Glu Glu Lys Leu Gln Ile Leu Thr Ala Leu 740 745 750 Cys His Arg Ile Leu Met Thr Tyr Ser Val Gln Asp His Met Glu Thr 755 760 765 Arg Gln Gln Met Ser Ala Glu Leu Trp Lys Glu Arg Leu Ala Val Leu 770 775 780 Lys Glu Glu Asn Asp Lys Lys Arg Ala Glu Lys Gln Lys Arg Lys Glu 785 790 795 800 Met Glu Ala Lys Asn Lys Glu Asn Gly Lys Val Glu Asn Gly Leu Gly 805 810 815 Lys Thr Asp Arg Lys Lys Arg Ile Val Lys Phe Glu Pro Gln Val Asp 820 825 830 Thr Glu Ala Glu Asp Met Ile Ser Ala Val Lys Ser Arg Arg Leu Leu 835 840 845 Ala Ile Gln Ala Lys Lys Glu Arg Glu Ile Gln Glu Arg Glu Met Lys 850 855 860 Val Lys Leu Glu Arg Gln Ala Glu Glu Glu Arg Ile Arg Lys His Lys 865 870 875 880 Ala Ala Ala Glu Lys Ala Phe Gln Glu Gly Ile Ala Lys Ala Lys Leu 885 890 895 Val Met Arg Arg Thr Pro Ile Gly Thr Asp Arg Asn His Asn Arg Tyr 900 905 910 Trp Leu Phe Ser Asp Glu Val Pro Gly Leu Phe Ile Glu Lys Gly Trp 915 920 925 Val His Asp Ser Ile Asp Tyr Arg Phe Asn His His Cys Lys Asp His 930 935 940 Thr Val Ser Gly Asp Glu Asp Tyr Cys Pro Arg Ser Lys Lys Ala Asn 945 950 955 960 Leu Gly Lys Asn Ala Ser Met Asn Thr Gln His Gly Thr Ala Thr Glu 965 970 975 Val Ala Val Glu Thr Thr Thr Pro Lys Gln Gly Gln Asn Leu Trp Phe 980 985 990 Leu Cys Asp Ser Gln Lys Glu Leu Asp Glu Leu Leu Asn Cys Leu His 995 1000 1005 Pro Gln Gly Ile Arg Glu Ser Gln Leu Lys Glu Arg Leu Glu Lys Arg 1010 1015 1020 Tyr Gln Asp Ile Ile His Ser Ile His Leu Ala Arg Lys Pro Asn Leu 1025 1030 1035 1040 Gly Leu Lys Ser Cys Asp Gly Asn Gln Glu Leu Leu Asn Phe Leu Arg 1045 1050 1055 Ser Asp Leu Ile Glu Val Ala Thr Arg Leu Gln Lys Gly Gly Leu Gly 1060 1065 1070 Tyr Val Glu Glu Thr Ser Glu Phe Glu Ala Arg Val Ile Ser Leu Glu 1075 1080 1085 Lys Leu Lys Asp Phe Gly Glu Cys Val Ile Ala Leu Gln Ala Ser Val 1090 1095 1100 Ile Lys Lys Phe Leu Gln Gly Phe Met Ala Pro Lys Gln Lys Arg Arg 1105 1110 1115 1120 Lys Leu Gln Ser Glu Asp Ser Ala Lys Thr Glu Glu Val Asp Glu Glu 1125 1130 1135 Lys Lys Met Val Glu Glu Ala Lys Val Ala Ser Ala Leu Glu Lys Trp 1140 1145 1150 Lys Thr Ala Ile Arg Glu Ala Gln Thr Phe Ser Arg Met His Val Leu 1155 1160 1165 Leu Gly Met Leu Asp Ala Cys Ile Lys Trp Asp Met Ser Ala Glu Asn 1170 1175 1180 Ala Arg Cys Lys Val Cys Pro Lys Lys Gly Glu Asp Asp Lys Leu Ile 1185 1190 1195 1200 Leu Cys Asp Glu Cys Asn Lys Ala Phe His Leu Phe Cys Leu Arg Pro 1205 1210 1215 Ala Leu Tyr Glu Val Pro Asp Gly Glu Trp Gln Cys Pro Ala Cys Gln 1220 1225 1230 Pro Ala Thr Ala Arg Arg Asn Ser Arg Gly Arg Asn Tyr Thr Glu Glu 1235 1240 1245 Ser Ala Ser Glu Asp Ser Glu Asp Asp Glu Ser Asp Glu Glu Glu Glu 1250 1255 1260 Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Tyr Glu Val Ala Gly Leu 1265 1270 1275 1280 Arg Leu Arg Pro Arg Lys Thr Ile Arg Gly Lys His Ser Val Ile Pro 1285 1290 1295 Pro Ala Ala Arg Ser Gly Arg Arg Pro Gly Lys Lys Pro His Ser Thr 1300 1305 1310 Arg Arg Ser Gln Pro Lys Ala Pro Pro Val Asp Asp Ala Glu Val Asp 1315 1320 1325 Glu Leu Val Leu Gln Thr Lys Arg Ser Ser Arg Arg Gln Ser Leu Glu 1330 1335 1340 Leu Gln Lys Cys Glu Glu Ile Leu His Lys Ile Val Lys Tyr Arg Phe 1345 1350 1355 1360 Ser Trp Pro Phe Arg Glu Pro Val Thr Arg Asp Glu Ala Glu Asp Tyr 1365 1370 1375 Tyr Asp Val Ile Thr His Pro Met Asp Phe Gln Thr Val Gln Asn Lys 1380 1385 1390 Cys Ser Cys Gly Ser Tyr Arg Ser Val Gln Glu Phe Leu Thr Asp Met 1395 1400 1405 Lys Gln Val Phe Thr Asn Ala Glu Val Tyr Asn Cys Arg Gly Ser His 1410 1415 1420 Val Leu Ser Cys Met Val Lys Thr Glu Gln Cys Leu Val Val Leu Leu 1425 1430 1435 1440 His Lys His Leu Pro Gly His Pro Tyr Val Arg Arg Lys Arg Lys Lys 1445 1450 1455 Phe Pro Asp Arg Leu Ala Glu Asp Glu Gly Asp Ser Glu Pro Glu Ala 1460 1465 1470 Val Gly Gln Ser Arg Asp Glu Asp Arg Arg Ser Arg Glu Ala Glu Ile 1475 1480 1485 Gln Glu Trp Leu Gln Asp Thr Ser Leu Tyr Ser Ala Lys Ile Asn Ser 1490 1495 1500 Lys Asp His Asn Cys Phe Met Met Leu Val Asn Thr Gln Phe Cys Met 1505 1510 1515 1520 Ala Leu Thr Asp Thr Val Thr 1525 28 5561 DNA Homo sapiens CDS (346)...(4926) 28 cgggcccggg ggaggagggg aatctcccgc catttttcaa taatttcctc cggtgctgct 60 gaggaggagt cgtgactgcc ggccgccggg acccgaagcg gaggtcggcg gggggctgct 120 gggaggcgcg gcggtgtgcg cgggagctct gcgccgtggc gttccgctcc atgactgtcg 180 cgcggccgcg ccggcggtga gggagccgga gttcgcgccg ccctctcacc cctcccttcc 240 cccaccccac ccccgggcgc ctggcgctcg ctccgggccg cggggcctag tgctgcgccg 300 cggggccggc cccagcagcc gccagtcccc accgccgccg ccgcg atg gcg ccg ctc 357 Met Ala Pro Leu 1 ctg ggc cgc aag ccc ttc ccg ctg gtg aat ccg ttg ccc gga gag gag 405 Leu Gly Arg Lys Pro Phe Pro Leu Val Asn Pro Leu Pro Gly Glu Glu 5 10 15 20 ccg ttc ttc acc atc ccg cac act cag gag gcc ttc cgc acc cgg gaa 453 Pro Phe Phe Thr Ile Pro His Thr Gln Glu Ala Phe Arg Thr Arg Glu 25 30 35 gag tat gaa gcc cgc ttg gaa agg tac agt gag cgc att tgg acg tgc 501 Glu Tyr Glu Ala Arg Leu Glu Arg Tyr Ser Glu Arg Ile Trp Thr Cys 40 45 50 aag agt act gga agc agt cag cta aca cac aag gaa gcc tgg gag gaa 549 Lys Ser Thr Gly Ser Ser Gln Leu Thr His Lys Glu Ala Trp Glu Glu 55 60 65 gaa cag gaa gtt gct gag ctt ttg aag gag gag ttt cct gcc tgg tat 597 Glu Gln Glu Val Ala Glu Leu Leu Lys Glu Glu Phe Pro Ala Trp Tyr 70 75 80 gag aag ctt gtt ctg gaa atg gtt cac cat aac aca gcc tcc tta gag 645 Glu Lys Leu Val Leu Glu Met Val His His Asn Thr Ala Ser Leu Glu 85 90 95 100 aag tta gta gat act gct tgg ttg gag atc atg acc aaa tat gct gtg 693 Lys Leu Val Asp Thr Ala Trp Leu Glu Ile Met Thr Lys Tyr Ala Val 105 110 115 gga gaa gag tgt gac ttc gag gtt ggg aag gag aaa atg ctc aag gtg 741 Gly Glu Glu Cys Asp Phe Glu Val Gly Lys Glu Lys Met Leu Lys Val 120 125 130 aag att gtg aag att cat cct ttg gag aaa gtg gat gaa gag gcc act 789 Lys Ile Val Lys Ile His Pro Leu Glu Lys Val Asp Glu Glu Ala Thr 135 140 145 gag aag aaa tct gat ggt gcc tgt gat tct cca tca agt gac aaa gag 837 Glu Lys Lys Ser Asp Gly Ala Cys Asp Ser Pro Ser Ser Asp Lys Glu 150 155 160 aac tcc agt cag att gct cag gac cat cag aag aag gag aca gtt gtg 885 Asn Ser Ser Gln Ile Ala Gln Asp His Gln Lys Lys Glu Thr Val Val 165 170 175 180 aaa gag gat gaa gga agg aga gag agt att aat gac aga gca cgt aga 933 Lys Glu Asp Glu Gly Arg Arg Glu Ser Ile Asn Asp Arg Ala Arg Arg 185 190 195 tcg cca cga aaa ctt cct act tca tta aaa aaa gga gaa agg aaa tgg 981 Ser Pro Arg Lys Leu Pro Thr Ser Leu Lys Lys Gly Glu Arg Lys Trp 200 205 210 gct cct cca aaa ttt ctg cct cac aaa tat gat gtg aaa cta caa aat 1029 Ala Pro Pro Lys Phe Leu Pro His Lys Tyr Asp Val Lys Leu Gln Asn 215 220 225 gaa gat aag atc atc agt aac gtg cca gca gac agc ttg att cgt aca 1077 Glu Asp Lys Ile Ile Ser Asn Val Pro Ala Asp Ser Leu Ile Arg Thr 230 235 240 gag cgc cca cca aat aag gag ata gtt cga tac ttt ata cgg cat aat 1125 Glu Arg Pro Pro Asn Lys Glu Ile Val Arg Tyr Phe Ile Arg His Asn 245 250 255 260 gca tta cga gct ggt act ggt gaa aat gca cct tgg gtc gta gaa gat 1173 Ala Leu Arg Ala Gly Thr Gly Glu Asn Ala Pro Trp Val Val Glu Asp 265 270 275 gaa ttg gtg aag aaa tac tct ctg ccc agc aag ttc agt gac ttt tta 1221 Glu Leu Val Lys Lys Tyr Ser Leu Pro Ser Lys Phe Ser Asp Phe Leu 280 285 290 ctt gat cca tac aag tat atg act ctc aac cct tct act aag agg aag 1269 Leu Asp Pro Tyr Lys Tyr Met Thr Leu Asn Pro Ser Thr Lys Arg Lys 295 300 305 aat act gga tcc cca gac agg aag ccc tca aag aaa tcc aag aca gac 1317 Asn Thr Gly Ser Pro Asp Arg Lys Pro Ser Lys Lys Ser Lys Thr Asp 310 315 320 aac tct tct ctt agt tca cca cta aat cct aag tta tgg tgt cac gta 1365 Asn Ser Ser Leu Ser Ser Pro Leu Asn Pro Lys Leu Trp Cys His Val 325 330 335 340 cac ttg aag aag tca ttg agt ggc tcg cca ctc aaa gtg aag aac tca 1413 His Leu Lys Lys Ser Leu Ser Gly Ser Pro Leu Lys Val Lys Asn Ser 345 350 355 aag aat tcc aaa tct cct gaa gaa cat cta gaa gaa atg atg aag atg 1461 Lys Asn Ser Lys Ser Pro Glu Glu His Leu Glu Glu Met Met Lys Met 360 365 370 atg tcg ccc aat aag ttg cac act aac ttt cac att cct aaa aaa ggc 1509 Met Ser Pro Asn Lys Leu His Thr Asn Phe His Ile Pro Lys Lys Gly 375 380 385 cca cct gcc aag aaa cca ggg aag cac agt gac aag cct ttg aag gca 1557 Pro Pro Ala Lys Lys Pro Gly Lys His Ser Asp Lys Pro Leu Lys Ala 390 395 400 aag ggc aga agc aaa ggc atc ctg aat gga cag aaa tcc aca ggg aat 1605 Lys Gly Arg Ser Lys Gly Ile Leu Asn Gly Gln Lys Ser Thr Gly Asn 405 410 415 420 tcc aaa tct ccc aaa aaa gga ctg aag act cct aaa acc aaa atg aag 1653 Ser Lys Ser Pro Lys Lys Gly Leu Lys Thr Pro Lys Thr Lys Met Lys 425 430 435 cag atg act ttg ttg gat atg gcc aaa ggc acg cag aag atg aca cga 1701 Gln Met Thr Leu Leu Asp Met Ala Lys Gly Thr Gln Lys Met Thr Arg 440 445 450 gcc cca cgg aat tct ggg ggt aca cct agg acc tct agt aaa cct cat 1749 Ala Pro Arg Asn Ser Gly Gly Thr Pro Arg Thr Ser Ser Lys Pro His 455 460 465 aaa cat ctg cct cct gca gcc cta cac ctc att gca tac tac aaa gaa 1797 Lys His Leu Pro Pro Ala Ala Leu His Leu Ile Ala Tyr Tyr Lys Glu 470 475 480 aac aaa gac agg gag gac aag agg agc gcc ctg tcc tgt gtt atc tcc 1845 Asn Lys Asp Arg Glu Asp Lys Arg Ser Ala Leu Ser Cys Val Ile Ser 485 490 495 500 aaa aca gct cgt ctt ctc tct agt gaa gat aga gct cgt ctc cca gaa 1893 Lys Thr Ala Arg Leu Leu Ser Ser Glu Asp Arg Ala Arg Leu Pro Glu 505 510 515 gaa ttg cga agt ctt gtt caa aaa cgc tat gaa ctt cta gag cac aaa 1941 Glu Leu Arg Ser Leu Val Gln Lys Arg Tyr Glu Leu Leu Glu His Lys 520 525 530 aag agg tgg gct tct atg tct gaa gaa caa cgg aaa gaa tat ttg aaa 1989 Lys Arg Trp Ala Ser Met Ser Glu Glu Gln Arg Lys Glu Tyr Leu Lys 535 540 545 aag aaa cgg gag gag ctg aaa aag aag ttg aag gaa aaa gcc aaa gaa 2037 Lys Lys Arg Glu Glu Leu Lys Lys Lys Leu Lys Glu Lys Ala Lys Glu 550 555 560 cga aga gag aaa gaa atg ctt gag aga tta gaa aaa cag aag cgg tat 2085 Arg Arg Glu Lys Glu Met Leu Glu Arg Leu Glu Lys Gln Lys Arg Tyr 565 570 575 580 gag gac caa gag tta act ggc aaa aac ctt cca gca ttc aga ttg gtg 2133 Glu Asp Gln Glu Leu Thr Gly Lys Asn Leu Pro Ala Phe Arg Leu Val 585 590 595 gat acc cct gaa ggg ctg ccc aac acg ctg ttt ggg gat gtg gcc atg 2181 Asp Thr Pro Glu Gly Leu Pro Asn Thr Leu Phe Gly Asp Val Ala Met 600 605 610 gtg gtg gaa ttc ttg agc tgt tat tct ggg cta ctt tta cca gat gct 2229 Val Val Glu Phe Leu Ser Cys Tyr Ser Gly Leu Leu Leu Pro Asp Ala 615 620 625 cag tat cct att act gct gtg tcc ctt atg gaa gcc ttg agt gca gat 2277 Gln Tyr Pro Ile Thr Ala Val Ser Leu Met Glu Ala Leu Ser Ala Asp 630 635 640 aag ggt ggc ttt tta tac ctt aac agg gtg ttg gtc atc ctc tta cag 2325 Lys Gly Gly Phe Leu Tyr Leu Asn Arg Val Leu Val Ile Leu Leu Gln 645 650 655 660 acc ctc cta caa gat gag ata gcc gaa gac tat ggt gaa ttg gga atg 2373 Thr Leu Leu Gln Asp Glu Ile Ala Glu Asp Tyr Gly Glu Leu Gly Met 665 670 675 aag ctg tca gaa atc ccc ttg act ctg cat tct gtt tca gag ctg gtg 2421 Lys Leu Ser Glu Ile Pro Leu Thr Leu His Ser Val Ser Glu Leu Val 680 685 690 cgg ctc tgc ttg cgc aga tct gat gtt cag gag gaa agc gag ggc tca 2469 Arg Leu Cys Leu Arg Arg Ser Asp Val Gln Glu Glu Ser Glu Gly Ser 695 700 705 gac aca gat gac aat aaa gat tca gct gca ttt gag gat aat gag gta 2517 Asp Thr Asp Asp Asn Lys Asp Ser Ala Ala Phe Glu Asp Asn Glu Val 710 715 720 caa gat gag ttc cta gaa aag ctg gag acc tct gaa ttt ttt gag ctg 2565 Gln Asp Glu Phe Leu Glu Lys Leu Glu Thr Ser Glu Phe Phe Glu Leu 725 730 735 740 acg tca gag gag aag cta cag att ttg aca gca ctg tgc cac cgg atc 2613 Thr Ser Glu Glu Lys Leu Gln Ile Leu Thr Ala Leu Cys His Arg Ile 745 750 755 ctc atg aca tac tca gtg caa gac cac atg gag acc aga cag cag atg 2661 Leu Met Thr Tyr Ser Val Gln Asp His Met Glu Thr Arg Gln Gln Met 760 765 770 tct gca gag ttg tgg aag gaa cgg ctt gct gtg ttg aag gaa gaa aat 2709 Ser Ala Glu Leu Trp Lys Glu Arg Leu Ala Val Leu Lys Glu Glu Asn 775 780 785 gat aag aag aga gca gag aaa cag aaa cgg aaa gaa atg gaa gcc aaa 2757 Asp Lys Lys Arg Ala Glu Lys Gln Lys Arg Lys Glu Met Glu Ala Lys 790 795 800 aat aaa gaa aat gga aaa gtt gag aat ggg tta ggc aaa act gat agg 2805 Asn Lys Glu Asn Gly Lys Val Glu Asn Gly Leu Gly Lys Thr Asp Arg 805 810 815 820 aaa aaa aga att gtg aag ttt gag ccc caa gta gat aca gaa gct gaa 2853 Lys Lys Arg Ile Val Lys Phe Glu Pro Gln Val Asp Thr Glu Ala Glu 825 830 835 gac atg att agt gct gtg aag agc aga agg ttg ctt gcc att caa gct 2901 Asp Met Ile Ser Ala Val Lys Ser Arg Arg Leu Leu Ala Ile Gln Ala 840 845 850 aag aag gaa cgg gaa atc cag gaa aga gaa atg aaa gtg aaa ctg gaa 2949 Lys Lys Glu Arg Glu Ile Gln Glu Arg Glu Met Lys Val Lys Leu Glu 855 860 865 cgc caa gct gaa gaa gaa cga ata cgg aag cac aaa gca gct gct gag 2997 Arg Gln Ala Glu Glu Glu Arg Ile Arg Lys His Lys Ala Ala Ala Glu 870 875 880 aaa gct ttc cag gaa ggg att gcc aag gcc aaa cta gtc atg cgc agg 3045 Lys Ala Phe Gln Glu Gly Ile Ala Lys Ala Lys Leu Val Met Arg Arg 885 890 895 900 act cct att ggc aca gat cga aac cat aat aga tac tgg ctc ttc tca 3093 Thr Pro Ile Gly Thr Asp Arg Asn His Asn Arg Tyr Trp Leu Phe Ser 905 910 915 gat gaa gtt cca gga tta ttc att gaa aaa ggc tgg gta cat gac agc 3141 Asp Glu Val Pro Gly Leu Phe Ile Glu Lys Gly Trp Val His Asp Ser 920 925 930 att gac tac cga ttc aac cat cac tgc aaa gac cac aca gtc tct ggt 3189 Ile Asp Tyr Arg Phe Asn His His Cys Lys Asp His Thr Val Ser Gly 935 940 945 gat gag gat tac tgt cct cgc agt aag aaa gca aac tta ggt aaa aat 3237 Asp Glu Asp Tyr Cys Pro Arg Ser Lys Lys Ala Asn Leu Gly Lys Asn 950 955 960 gca agc atg aac aca caa cat gga aca gca aca gaa gtt gct gta gag 3285 Ala Ser Met Asn Thr Gln His Gly Thr Ala Thr Glu Val Ala Val Glu 965 970 975 980 aca acc aca ccc aaa caa gga cag aac cta tgg ttt tta tgt gat agt 3333 Thr Thr Thr Pro Lys Gln Gly Gln Asn Leu Trp Phe Leu Cys Asp Ser 985 990 995 caa aag gag ctg gat gag ttg cta aac tgt ctt cac cct cag gga ata 3381 Gln Lys Glu Leu Asp Glu Leu Leu Asn Cys Leu His Pro Gln Gly Ile 1000 1005 1010 aga gaa agt caa ctt aaa gag aga cta gag aag agg tac cag gac att 3429 Arg Glu Ser Gln Leu Lys Glu Arg Leu Glu Lys Arg Tyr Gln Asp Ile 1015 1020 1025 att cac tct att cat cta gca cgg aag cca aat ttg ggt cta aaa tct 3477 Ile His Ser Ile His Leu Ala Arg Lys Pro Asn Leu Gly Leu Lys Ser 1030 1035 1040 tgt gat ggc aac cag gag ctt tta aac ttc ctt cgt agt gat ctc att 3525 Cys Asp Gly Asn Gln Glu Leu Leu Asn Phe Leu Arg Ser Asp Leu Ile 1045 1050 1055 1060 gaa gtt gca aca agg tta caa aaa gga gga ctt gga tat gtg gaa gaa 3573 Glu Val Ala Thr Arg Leu Gln Lys Gly Gly Leu Gly Tyr Val Glu Glu 1065 1070 1075 aca tca gaa ttt gaa gcc cgg gtc att tca tta gag aaa ttg aag gat 3621 Thr Ser Glu Phe Glu Ala Arg Val Ile Ser Leu Glu Lys Leu Lys Asp 1080 1085 1090 ttt ggt gag tgt gtg att gcc ctt cag gcc agt gtc ata aag aaa ttt 3669 Phe Gly Glu Cys Val Ile Ala Leu Gln Ala Ser Val Ile Lys Lys Phe 1095 1100 1105 ctc caa ggc ttc atg gct ccc aag caa aag aga aga aaa ctc caa agt 3717 Leu Gln Gly Phe Met Ala Pro Lys Gln Lys Arg Arg Lys Leu Gln Ser 1110 1115 1120 gaa gat tca gca aaa act gag gaa gtg gat gaa gag aag aaa atg gta 3765 Glu Asp Ser Ala Lys Thr Glu Glu Val Asp Glu Glu Lys Lys Met Val 1125 1130 1135 1140 gag gaa gca aag gtt gca tct gca ctg gag aaa tgg aag aca gca atc 3813 Glu Glu Ala Lys Val Ala Ser Ala Leu Glu Lys Trp Lys Thr Ala Ile 1145 1150 1155 cgg gaa gct cag act ttc tcc agg atg cac gtg ctg ctt ggg atg ctt 3861 Arg Glu Ala Gln Thr Phe Ser Arg Met His Val Leu Leu Gly Met Leu 1160 1165 1170 gat gcc tgt atc aag tgg gat atg tcc gca gaa aat gct agg tgc aaa 3909 Asp Ala Cys Ile Lys Trp Asp Met Ser Ala Glu Asn Ala Arg Cys Lys 1175 1180 1185 gtt tgt cca aag aaa ggt gag gat gac aaa ttg atc ttg tgt gat gag 3957 Val Cys Pro Lys Lys Gly Glu Asp Asp Lys Leu Ile Leu Cys Asp Glu 1190 1195 1200 tgt aat aaa gcc ttc cac ctg ttt tgt ctg agg ccg gcc ctc tat gaa 4005 Cys Asn Lys Ala Phe His Leu Phe Cys Leu Arg Pro Ala Leu Tyr Glu 1205 1210 1215 1220 gta cca gat ggt gag tgg cag tgc cca gct tgc cag ccc gct act gcc 4053 Val Pro Asp Gly Glu Trp Gln Cys Pro Ala Cys Gln Pro Ala Thr Ala 1225 1230 1235 agg cgc aac tcc cgt ggc agg aac tat act gaa gag tct gct tct gag 4101 Arg Arg Asn Ser Arg Gly Arg Asn Tyr Thr Glu Glu Ser Ala Ser Glu 1240 1245 1250 gac agt gaa gat gat gag agt gat gaa gag gag gag gag gaa gaa gag 4149 Asp Ser Glu Asp Asp Glu Ser Asp Glu Glu Glu Glu Glu Glu Glu Glu 1255 1260 1265 gag gag gag gaa gaa gat tat gag gtg gct ggt ttg cga ttg aga cct 4197 Glu Glu Glu Glu Glu Asp Tyr Glu Val Ala Gly Leu Arg Leu Arg Pro 1270 1275 1280 cga aag acc atc cgg ggc aag cac agc gtc atc ccc cct gca gca agg 4245 Arg Lys Thr Ile Arg Gly Lys His Ser Val Ile Pro Pro Ala Ala Arg 1285 1290 1295 1300 tca ggc cgg cgc ccg ggt aag aag cca cac tct acc agg agg tct cag 4293 Ser Gly Arg Arg Pro Gly Lys Lys Pro His Ser Thr Arg Arg Ser Gln 1305 1310 1315 ccc aag gca cca cct gtg gat gat gct gag gtg gat gag ctg gtg ctt 4341 Pro Lys Ala Pro Pro Val Asp Asp Ala Glu Val Asp Glu Leu Val Leu 1320 1325 1330 cag acc aag cgg agc tcc cgg agg caa agc ctg gag ctg cag aag tgt 4389 Gln Thr Lys Arg Ser Ser Arg Arg Gln Ser Leu Glu Leu Gln Lys Cys 1335 1340 1345 gaa gag atc ctc cac aag atc gtg aag tac cgc ttc agc tgg ccc ttc 4437 Glu Glu Ile Leu His Lys Ile Val Lys Tyr Arg Phe Ser Trp Pro Phe 1350 1355 1360 agg gag cct gtg acc aga gat gag gcc gag gac tac tat gat gtg atc 4485 Arg Glu Pro Val Thr Arg Asp Glu Ala Glu Asp Tyr Tyr Asp Val Ile 1365 1370 1375 1380 acg cac ccc atg gac ttt cag aca gtg cag aac aaa tgt tcc tgt ggg 4533 Thr His Pro Met Asp Phe Gln Thr Val Gln Asn Lys Cys Ser Cys Gly 1385 1390 1395 agc tac cgc tct gtg cag gag ttt ctt act gac atg aag caa gtg ttt 4581 Ser Tyr Arg Ser Val Gln Glu Phe Leu Thr Asp Met Lys Gln Val Phe 1400 1405 1410 acc aat gct gag gtt tac aac tgc cgt ggc agc cat gtg cta agc tgc 4629 Thr Asn Ala Glu Val Tyr Asn Cys Arg Gly Ser His Val Leu Ser Cys 1415 1420 1425 atg gtg aag aca gaa cag tgt cta gtg gtt ctg ttg cat aaa cac ctt 4677 Met Val Lys Thr Glu Gln Cys Leu Val Val Leu Leu His Lys His Leu 1430 1435 1440 cct ggc cac cca tat gtc cgc agg aag cgc aag aag ttt cct gat agg 4725 Pro Gly His Pro Tyr Val Arg Arg Lys Arg Lys Lys Phe Pro Asp Arg 1445 1450 1455 1460 ctt gct gaa gat gaa ggg gac agt gag cca gag gcc gtt gga cag tcc 4773 Leu Ala Glu Asp Glu Gly Asp Ser Glu Pro Glu Ala Val Gly Gln Ser 1465 1470 1475 agg gac gaa gac aga aga agt aga gag gcg gag att cag gaa tgg ctc 4821 Arg Asp Glu Asp Arg Arg Ser Arg Glu Ala Glu Ile Gln Glu Trp Leu 1480 1485 1490 cag gac acg tcc ctt tac tct gcc aag atc aac tca aaa gac cac aac 4869 Gln Asp Thr Ser Leu Tyr Ser Ala Lys Ile Asn Ser Lys Asp His Asn 1495 1500 1505 tgt ttc atg atg ctg gtg aat aca caa ttc tgt atg gca ctc act gat 4917 Cys Phe Met Met Leu Val Asn Thr Gln Phe Cys Met Ala Leu Thr Asp 1510 1515 1520 act gtc acc tgagaggaag acgggggaag agacagagta tgggcttaaa 4966 Thr Val Thr 1525 gaaacaagac tgtataataa atacagatta aaaaagaaaa atcgccacca tctcccctgt 5026 tggcctgatt accccgatcc tgctatgtaa cacagcaatc cctcccctgg agaccagagg 5086 ggcttggcac tgtggtggaa gccagaacga gcaggccctt aggaaagaag gcaggaacag 5146 gaactggctt caccagaaaa gctagaccct cggactcctc ctggaaactc tcagaaggga 5206 gggttatggc cctctttgtc ccttcatatt tctggacaaa gaccaccaac ccaatatcaa 5266 gccccataaa gagcttttag aaaaacagca taagcttggg atgacaggcg tttctggact 5326 ccctgtgatc tcttccaggt tcttggtctt cctcgctcgc ctccctccca ccctccctag 5386 ctgtcccccc acctcagctc ccttaccacg gccctgcctc tctacttctt ctgtcttcgt 5446 cccctggact gtccaacggc ctctggctca ctgtcccttc atcttcagca acctatcagg 5506 aaacttcttg cgcttcctgc ggacatatgg gtggccagga agtgtttatg caaca 5561 29 1531 PRT Homo sapiens 29 Met Ala Pro Leu Leu Gly Arg Lys Pro Phe Pro Leu Val Asn Pro Leu 1 5 10 15 Pro Gly Glu Glu Pro Phe Phe Thr Ile Pro His Thr Gln Glu Ala Phe 20 25 30 Arg Thr Arg Glu Glu Tyr Glu Ala Arg Leu Glu Arg Tyr Ser Glu Arg 35 40 45 Ile Trp Thr Cys Lys Ser Thr Gly Ser Ser Gln Leu Thr His Lys Glu 50 55 60 Ala Trp Glu Glu Glu Gln Glu Val Ala Glu Leu Leu Lys Glu Glu Phe 65 70 75 80 Pro Ala Trp Tyr Glu Lys Leu Val Leu Glu Met Val His His Asn Thr 85 90 95 Ala Ser Leu Glu Lys Leu Val Asp Thr Ala Trp Leu Glu Ile Met Thr 100 105 110 Lys Tyr Ala Val Gly Glu Glu Cys Asp Phe Glu Val Gly Lys Glu Lys 115 120 125 Met Leu Lys Val Lys Ile Val Lys Ile His Pro Leu Glu Lys Val Asp 130 135 140 Glu Glu Ala Thr Glu Lys Lys Ser Asp Gly Ala Cys Asp Ser Pro Ser 145 150 155 160 Ser Asp Lys Glu Asn Ser Ser Gln Ile Ala Gln Asp His Gln Lys Lys 165 170 175 Glu Thr Val Val Lys Glu Asp Glu Gly Arg Arg Glu Ser Ile Asn Asp 180 185 190 Arg Ala Arg Arg Ser Pro Arg Lys Leu Pro Thr Ser Leu Lys Lys Gly 195 200 205 Glu Arg Lys Trp Ala Pro Pro Lys Phe Leu Pro His Lys Tyr Asp Val 210 215 220 Lys Leu Gln Asn Glu Asp Lys Ile Ile Ser Asn Val Pro Ala Asp Ser 225 230 235 240 Leu Ile Arg Thr Glu Arg Pro Pro Asn Lys Glu Ile Val Arg Tyr Phe 245 250 255 Ile Arg His Asn Ala Leu Arg Ala Gly Thr Gly Glu Asn Ala Pro Trp 260 265 270 Val Val Glu Asp Glu Leu Val Lys Lys Tyr Ser Leu Pro Ser Lys Phe 275 280 285 Ser Asp Phe Leu Leu Asp Pro Tyr Lys Tyr Met Thr Leu Asn Pro Ser 290 295 300 Thr Lys Arg Lys Asn Thr Gly Ser Pro Asp Arg Lys Pro Ser Lys Lys 305 310 315 320 Ser Lys Thr Asp Asn Ser Ser Leu Ser Ser Pro Leu Asn Pro Lys Leu 325 330 335 Trp Cys His Val His Leu Lys Lys Ser Leu Ser Gly Ser Pro Leu Lys 340 345 350 Val Lys Asn Ser Lys Asn Ser Lys Ser Pro Glu Glu His Leu Glu Glu 355 360 365 Met Met Lys Met Met Ser Pro Asn Lys Leu His Thr Asn Phe His Ile 370 375 380 Pro Lys Lys Gly Pro Pro Ala Lys Lys Pro Gly Lys His Ser Asp Lys 385 390 395 400 Pro Leu Lys Ala Lys Gly Arg Ser Lys Gly Ile Leu Asn Gly Gln Lys 405 410 415 Ser Thr Gly Asn Ser Lys Ser Pro Lys Lys Gly Leu Lys Thr Pro Lys 420 425 430 Thr Lys Met Lys Gln Met Thr Leu Leu Asp Met Ala Lys Gly Thr Gln 435 440 445 Lys Met Thr Arg Ala Pro Arg Asn Ser Gly Gly Thr Pro Arg Thr Ser 450 455 460 Ser Lys Pro His Lys His Leu Pro Pro Ala Ala Leu His Leu Ile Ala 465 470 475 480 Tyr Tyr Lys Glu Asn Lys Asp Arg Glu Asp Lys Arg Ser Ala Leu Ser 485 490 495 Cys Val Ile Ser Lys Thr Ala Arg Leu Leu Ser Ser Glu Asp Arg Ala 500 505 510 Arg Leu Pro Glu Glu Leu Arg Ser Leu Val Gln Lys Arg Tyr Glu Leu 515 520 525 Leu Glu His Lys Lys Arg Trp Ala Ser Met Ser Glu Glu Gln Arg Lys 530 535 540 Glu Tyr Leu Lys Lys Lys Arg Glu Glu Leu Lys Lys Lys Leu Lys Glu 545 550 555 560 Lys Ala Lys Glu Arg Arg Glu Lys Glu Met Leu Glu Arg Leu Glu Lys 565 570 575 Gln Lys Arg Tyr Glu Asp Gln Glu Leu Thr Gly Lys Asn Leu Pro Ala 580 585 590 Phe Arg Leu Val Asp Thr Pro Glu Gly Leu Pro Asn Thr Leu Phe Gly 595 600 605 Asp Val Ala Met Val Val Glu Phe Leu Ser Cys Tyr Ser Gly Leu Leu 610 615 620 Leu Pro Asp Ala Gln Tyr Pro Ile Thr Ala Val Ser Leu Met Glu Ala 625 630 635 640 Leu Ser Ala Asp Lys Gly Gly Phe Leu Tyr Leu Asn Arg Val Leu Val 645 650 655 Ile Leu Leu Gln Thr Leu Leu Gln Thr Leu Leu Gln Asp Glu Ile Ala 660 665 670 Glu Asp Tyr Gly Glu Leu Gly Met Lys Leu Ser Glu Ile Pro Leu Thr 675 680 685 Leu His Ser Val Ser Glu Leu Val Arg Leu Cys Leu Arg Arg Ser Asp 690 695 700 Val Gln Glu Glu Ser Glu Gly Ser Asp Thr Asp Asp Asn Lys Asp Ser 705 710 715 720 Ala Ala Phe Glu Asp Asn Glu Val Gln Asp Glu Phe Leu Glu Lys Leu 725 730 735 Glu Thr Ser Glu Phe Phe Glu Leu Thr Ser Glu Glu Lys Leu Gln Ile 740 745 750 Leu Thr Ala Leu Cys His Arg Ile Leu Met Thr Tyr Ser Val Gln Asp 755 760 765 His Met Glu Thr Arg Gln Gln Met Ser Ala Glu Leu Trp Lys Glu Arg 770 775 780 Leu Ala Val Leu Lys Glu Glu Asn Asp Lys Lys Arg Ala Glu Lys Gln 785 790 795 800 Lys Arg Lys Glu Met Glu Ala Lys Asn Lys Glu Asn Gly Lys Val Glu 805 810 815 Asn Gly Leu Gly Lys Thr Asp Arg Lys Lys Arg Ile Val Lys Phe Glu 820 825 830 Pro Gln Val Asp Thr Glu Ala Glu Asp Met Ile Ser Ala Val Lys Ser 835 840 845 Arg Arg Leu Leu Ala Ile Gln Ala Lys Lys Glu Arg Glu Ile Gln Glu 850 855 860 Arg Glu Met Lys Val Lys Leu Glu Arg Gln Ala Glu Glu Glu Arg Ile 865 870 875 880 Arg Lys His Lys Ala Ala Ala Glu Lys Ala Phe Gln Glu Gly Ile Ala 885 890 895 Lys Ala Lys Leu Val Met Arg Arg Thr Pro Ile Gly Thr Asp Arg Asn 900 905 910 His Asn Arg Tyr Trp Leu Phe Ser Asp Glu Val Pro Gly Leu Phe Ile 915 920 925 Glu Lys Gly Trp Val His Asp Ser Ile Asp Tyr Arg Phe Asn His His 930 935 940 Cys Lys Asp His Thr Val Ser Gly Asp Glu Asp Tyr Cys Pro Arg Ser 945 950 955 960 Lys Lys Ala Asn Leu Gly Lys Asn Ala Ser Met Asn Thr Gln His Gly 965 970 975 Thr Ala Thr Glu Val Ala Val Glu Thr Thr Thr Pro Lys Gln Gly Gln 980 985 990 Asn Leu Trp Phe Leu Cys Asp Ser Gln Lys Glu Leu Asp Glu Leu Leu 995 1000 1005 Asn Cys Leu His Pro Gln Gly Ile Arg Glu Ser Gln Leu Lys Glu Arg 1010 1015 1020 Leu Glu Lys Arg Tyr Gln Asp Ile Ile His Ser Ile His Leu Ala Arg 1025 1030 1035 1040 Lys Pro Asn Leu Gly Leu Lys Ser Cys Asp Gly Asn Gln Glu Leu Leu 1045 1050 1055 Asn Phe Leu Arg Ser Asp Leu Ile Glu Val Ala Thr Arg Leu Gln Lys 1060 1065 1070 Gly Gly Leu Gly Tyr Val Glu Glu Thr Ser Glu Phe Glu Ala Arg Val 1075 1080 1085 Ile Ser Leu Glu Lys Leu Lys Asp Phe Gly Glu Cys Val Ile Ala Leu 1090 1095 1100 Gln Ala Ser Val Ile Lys Lys Phe Leu Gln Gly Phe Met Ala Pro Lys 1105 1110 1115 1120 Gln Lys Arg Arg Lys Leu Gln Ser Glu Asp Ser Ala Lys Thr Glu Glu 1125 1130 1135 Val Asp Glu Glu Lys Lys Met Val Glu Glu Ala Lys Val Ala Ser Ala 1140 1145 1150 Leu Glu Lys Trp Lys Thr Ala Ile Arg Glu Ala Gln Thr Phe Ser Arg 1155 1160 1165 Met His Val Leu Leu Gly Met Leu Asp Ala Cys Ile Lys Trp Asp Met 1170 1175 1180 Ser Ala Glu Asn Ala Arg Cys Lys Val Cys Pro Lys Lys Gly Glu Asp 1185 1190 1195 1200 Asp Lys Leu Ile Leu Cys Asp Glu Cys Asn Lys Ala Phe His Leu Phe 1205 1210 1215 Cys Leu Arg Pro Ala Leu Tyr Glu Val Pro Asp Gly Glu Trp Gln Cys 1220 1225 1230 Pro Ala Cys Gln Pro Ala Thr Ala Arg Arg Asn Ser Arg Gly Arg Asn 1235 1240 1245 Tyr Thr Glu Glu Ser Ala Ser Glu Asp Ser Glu Asp Asp Glu Ser Asp 1250 1255 1260 Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Tyr Glu 1265 1270 1275 1280 Val Ala Gly Leu Arg Leu Arg Pro Arg Lys Thr Ile Arg Gly Lys His 1285 1290 1295 Ser Val Ile Pro Pro Ala Ala Arg Ser Gly Arg Arg Pro Gly Lys Lys 1300 1305 1310 Pro His Ser Thr Arg Arg Ser Gln Pro Lys Ala Pro Pro Val Asp Asp 1315 1320 1325 Ala Glu Val Asp Glu Leu Val Leu Gln Thr Lys Arg Ser Ser Arg Arg 1330 1335 1340 Gln Ser Leu Glu Leu Gln Lys Cys Glu Glu Ile Leu His Lys Ile Val 1345 1350 1355 1360 Lys Tyr Arg Phe Ser Trp Pro Phe Arg Glu Pro Val Thr Arg Asp Glu 1365 1370 1375 Ala Glu Asp Tyr Tyr Asp Val Ile Thr His Pro Met Asp Phe Gln Thr 1380 1385 1390 Val Gln Asn Lys Cys Ser Cys Gly Ser Tyr Arg Ser Val Gln Glu Phe 1395 1400 1405 Leu Thr Asp Met Lys Gln Val Phe Thr Asn Ala Glu Val Tyr Asn Cys 1410 1415 1420 Arg Gly Ser His Val Leu Ser Cys Met Val Lys Thr Glu Gln Cys Leu 1425 1430 1435 1440 Val Val Leu Leu His Lys His Leu Pro Gly His Pro Tyr Val Arg Arg 1445 1450 1455 Lys Arg Lys Lys Phe Pro Asp Arg Leu Ala Glu Asp Glu Gly Asp Ser 1460 1465 1470 Glu Pro Glu Ala Val Gly Gln Ser Arg Asp Glu Asp Arg Arg Ser Arg 1475 1480 1485 Glu Ala Glu Ile Gln Glu Trp Leu Gln Asp Thr Ser Leu Tyr Ser Ala 1490 1495 1500 Lys Ile Asn Ser Lys Asp His Asn Cys Phe Met Met Leu Val Asn Thr 1505 1510 1515 1520 Gln Phe Cys Met Ala Leu Thr Asp Thr Val Thr 1525 1530 30 5573 DNA Homo sapiens CDS (346)...(4938) 30 cgggcccggg ggaggagggg aatctcccgc catttttcaa taatttcctc cggtgctgct 60 gaggaggagt cgtgactgcc ggccgccggg acccgaagcg gaggtcggcg gggggctgct 120 gggaggcgcg gcggtgtgcg cgggagctct gcgccgtggc gttccgctcc atgactgtcg 180 cgcggccgcg ccggcggtga gggagccgga gttcgcgccg ccctctcacc cctcccttcc 240 cccaccccac ccccgggcgc ctggcgctcg ctccgggccg cggggcctag tgctgcgccg 300 cggggccggc cccagcagcc gccagtcccc accgccgccg ccgcg atg gcg ccg ctc 357 Met Ala Pro Leu 1 ctg ggc cgc aag ccc ttc ccg ctg gtg aat ccg ttg ccc gga gag gag 405 Leu Gly Arg Lys Pro Phe Pro Leu Val Asn Pro Leu Pro Gly Glu Glu 5 10 15 20 ccg ttc ttc acc atc ccg cac act cag gag gcc ttc cgc acc cgg gaa 453 Pro Phe Phe Thr Ile Pro His Thr Gln Glu Ala Phe Arg Thr Arg Glu 25 30 35 gag tat gaa gcc cgc ttg gaa agg tac agt gag cgc att tgg acg tgc 501 Glu Tyr Glu Ala Arg Leu Glu Arg Tyr Ser Glu Arg Ile Trp Thr Cys 40 45 50 aag agt act gga agc agt cag cta aca cac aag gaa gcc tgg gag gaa 549 Lys Ser Thr Gly Ser Ser Gln Leu Thr His Lys Glu Ala Trp Glu Glu 55 60 65 gaa cag gaa gtt gct gag ctt ttg aag gag gag ttt cct gcc tgg tat 597 Glu Gln Glu Val Ala Glu Leu Leu Lys Glu Glu Phe Pro Ala Trp Tyr 70 75 80 gag aag ctt gtt ctg gaa atg gtt cac cat aac aca gcc tcc tta gag 645 Glu Lys Leu Val Leu Glu Met Val His His Asn Thr Ala Ser Leu Glu 85 90 95 100 aag tta gta gat act gct tgg ttg gag atc atg acc aaa tat gct gtg 693 Lys Leu Val Asp Thr Ala Trp Leu Glu Ile Met Thr Lys Tyr Ala Val 105 110 115 gga gaa gag tgt gac ttc gag gtt ggg aag gag aaa atg ctc aag gtg 741 Gly Glu Glu Cys Asp Phe Glu Val Gly Lys Glu Lys Met Leu Lys Val 120 125 130 aag att gtg aag att cat cct ttg gag aaa gtg gat gaa gag gcc act 789 Lys Ile Val Lys Ile His Pro Leu Glu Lys Val Asp Glu Glu Ala Thr 135 140 145 gag aag aaa tct gat ggt gcc tgt gat tct cca tca agt gac aaa gag 837 Glu Lys Lys Ser Asp Gly Ala Cys Asp Ser Pro Ser Ser Asp Lys Glu 150 155 160 aac tcc agt cag att gct cag gac cat cag aag aag gag aca gtt gtg 885 Asn Ser Ser Gln Ile Ala Gln Asp His Gln Lys Lys Glu Thr Val Val 165 170 175 180 aaa gag gat gaa gga agg aga gag agt att aat gac aga gca cgt aga 933 Lys Glu Asp Glu Gly Arg Arg Glu Ser Ile Asn Asp Arg Ala Arg Arg 185 190 195 tcg cca cga aaa ctt cct act tca tta aaa aaa gga gaa agg aaa tgg 981 Ser Pro Arg Lys Leu Pro Thr Ser Leu Lys Lys Gly Glu Arg Lys Trp 200 205 210 gct cct cca aaa ttt ctg cct cac aaa tat gat gtg aaa cta caa aat 1029 Ala Pro Pro Lys Phe Leu Pro His Lys Tyr Asp Val Lys Leu Gln Asn 215 220 225 gaa gat aag atc atc agt aac gtg cca gca gac agc ttg att cgt aca 1077 Glu Asp Lys Ile Ile Ser Asn Val Pro Ala Asp Ser Leu Ile Arg Thr 230 235 240 gag cgc cca cca aat aag gag ata gtt cga tac ttt ata cgg cat aat 1125 Glu Arg Pro Pro Asn Lys Glu Ile Val Arg Tyr Phe Ile Arg His Asn 245 250 255 260 gca tta cga gct ggt act ggt gaa aat gca cct tgg gtc gta gaa gat 1173 Ala Leu Arg Ala Gly Thr Gly Glu Asn Ala Pro Trp Val Val Glu Asp 265 270 275 gaa ttg gtg aag aaa tac tct ctg ccc agc aag ttc agt gac ttt tta 1221 Glu Leu Val Lys Lys Tyr Ser Leu Pro Ser Lys Phe Ser Asp Phe Leu 280 285 290 ctt gat cca tac aag tat atg act ctc aac cct tct act aag agg aag 1269 Leu Asp Pro Tyr Lys Tyr Met Thr Leu Asn Pro Ser Thr Lys Arg Lys 295 300 305 aat act gga tcc cca gac agg aag ccc tca aag aaa tcc aag aca gac 1317 Asn Thr Gly Ser Pro Asp Arg Lys Pro Ser Lys Lys Ser Lys Thr Asp 310 315 320 aac tct tct ctt agt tca cca cta aat cct aag tta tgg tgt cac gta 1365 Asn Ser Ser Leu Ser Ser Pro Leu Asn Pro Lys Leu Trp Cys His Val 325 330 335 340 cac ttg aag aag tca ttg agt ggc tcg cca ctc aaa gtg aag aac tca 1413 His Leu Lys Lys Ser Leu Ser Gly Ser Pro Leu Lys Val Lys Asn Ser 345 350 355 aag aat tcc aaa tct cct gaa gaa cat cta gaa gaa atg atg aag atg 1461 Lys Asn Ser Lys Ser Pro Glu Glu His Leu Glu Glu Met Met Lys Met 360 365 370 atg tcg ccc aat aag ttg cac act aac ttt cac att cct aaa aaa ggc 1509 Met Ser Pro Asn Lys Leu His Thr Asn Phe His Ile Pro Lys Lys Gly 375 380 385 cca cct gcc aag aaa cca ggg aag cac agt gac aag cct ttg aag gca 1557 Pro Pro Ala Lys Lys Pro Gly Lys His Ser Asp Lys Pro Leu Lys Ala 390 395 400 aag ggc aga agc aaa ggc atc ctg aat gga cag aaa tcc aca ggg aat 1605 Lys Gly Arg Ser Lys Gly Ile Leu Asn Gly Gln Lys Ser Thr Gly Asn 405 410 415 420 tcc aaa tct ccc aaa aaa gga ctg aag act cct aaa acc aaa atg aag 1653 Ser Lys Ser Pro Lys Lys Gly Leu Lys Thr Pro Lys Thr Lys Met Lys 425 430 435 cag atg act ttg ttg gat atg gcc aaa ggc acg cag aag atg aca cga 1701 Gln Met Thr Leu Leu Asp Met Ala Lys Gly Thr Gln Lys Met Thr Arg 440 445 450 gcc cca cgg aat tct ggg ggt aca cct agg acc tct agt aaa cct cat 1749 Ala Pro Arg Asn Ser Gly Gly Thr Pro Arg Thr Ser Ser Lys Pro His 455 460 465 aaa cat ctg cct cct gca gcc cta cac ctc att gca tac tac aaa gaa 1797 Lys His Leu Pro Pro Ala Ala Leu His Leu Ile Ala Tyr Tyr Lys Glu 470 475 480 aac aaa gac agg gag gac aag agg agc gcc ctg tcc tgt gtt atc tcc 1845 Asn Lys Asp Arg Glu Asp Lys Arg Ser Ala Leu Ser Cys Val Ile Ser 485 490 495 500 aaa aca gct cgt ctt ctc tct agt gaa gat aga gct cgt ctc cca gaa 1893 Lys Thr Ala Arg Leu Leu Ser Ser Glu Asp Arg Ala Arg Leu Pro Glu 505 510 515 gaa ttg cga agt ctt gtt caa aaa cgc tat gaa ctt cta gag cac aaa 1941 Glu Leu Arg Ser Leu Val Gln Lys Arg Tyr Glu Leu Leu Glu His Lys 520 525 530 aag agg tgg gct tct atg tct gaa gaa caa cgg aaa gaa tat ttg aaa 1989 Lys Arg Trp Ala Ser Met Ser Glu Glu Gln Arg Lys Glu Tyr Leu Lys 535 540 545 aag aaa cgg gag gag ctg aaa aag aag ttg aag gaa aaa gcc aaa gaa 2037 Lys Lys Arg Glu Glu Leu Lys Lys Lys Leu Lys Glu Lys Ala Lys Glu 550 555 560 cga aga gag aaa gaa atg ctt gag aga tta gaa aaa cag aag cgg tat 2085 Arg Arg Glu Lys Glu Met Leu Glu Arg Leu Glu Lys Gln Lys Arg Tyr 565 570 575 580 gag gac caa gag tta act ggc aaa aac ctt cca gca ttc aga ttg gtg 2133 Glu Asp Gln Glu Leu Thr Gly Lys Asn Leu Pro Ala Phe Arg Leu Val 585 590 595 gat acc cct gaa ggg ctg ccc aac acg ctg ttt ggg gat gtg gcc atg 2181 Asp Thr Pro Glu Gly Leu Pro Asn Thr Leu Phe Gly Asp Val Ala Met 600 605 610 gtg gtg gaa ttc ttg agc tgt tat tct ggg cta ctt tta cca gat gct 2229 Val Val Glu Phe Leu Ser Cys Tyr Ser Gly Leu Leu Leu Pro Asp Ala 615 620 625 cag tat cct att act gct gtg tcc ctt atg gaa gcc ttg agt gca gat 2277 Gln Tyr Pro Ile Thr Ala Val Ser Leu Met Glu Ala Leu Ser Ala Asp 630 635 640 aag ggt ggc ttt tta tac ctt aac agg gtg ttg gtc atc ctc tta cag 2325 Lys Gly Gly Phe Leu Tyr Leu Asn Arg Val Leu Val Ile Leu Leu Gln 645 650 655 660 acc ctc cta cag acc ctc cta caa gat gag ata gcc gaa gac tat ggt 2373 Thr Leu Leu Gln Thr Leu Leu Gln Asp Glu Ile Ala Glu Asp Tyr Gly 665 670 675 gaa ttg gga atg aag ctg tca gaa atc ccc ttg act ctg cat tct gtt 2421 Glu Leu Gly Met Lys Leu Ser Glu Ile Pro Leu Thr Leu His Ser Val 680 685 690 tca gag ctg gtg cgg ctc tgc ttg cgc aga tct gat gtt cag gag gaa 2469 Ser Glu Leu Val Arg Leu Cys Leu Arg Arg Ser Asp Val Gln Glu Glu 695 700 705 agc gag ggc tca gac aca gat gac aat aaa gat tca gct gca ttt gag 2517 Ser Glu Gly Ser Asp Thr Asp Asp Asn Lys Asp Ser Ala Ala Phe Glu 710 715 720 gat aat gag gta caa gat gag ttc cta gaa aag ctg gag acc tct gaa 2565 Asp Asn Glu Val Gln Asp Glu Phe Leu Glu Lys Leu Glu Thr Ser Glu 725 730 735 740 ttt ttt gag ctg acg tca gag gag aag cta cag att ttg aca gca ctg 2613 Phe Phe Glu Leu Thr Ser Glu Glu Lys Leu Gln Ile Leu Thr Ala Leu 745 750 755 tgc cac cgg atc ctc atg aca tac tca gtg caa gac cac atg gag acc 2661 Cys His Arg Ile Leu Met Thr Tyr Ser Val Gln Asp His Met Glu Thr 760 765 770 aga cag cag atg tct gca gag ttg tgg aag gaa cgg ctt gct gtg ttg 2709 Arg Gln Gln Met Ser Ala Glu Leu Trp Lys Glu Arg Leu Ala Val Leu 775 780 785 aag gaa gaa aat gat aag aag aga gca gag aaa cag aaa cgg aaa gaa 2757 Lys Glu Glu Asn Asp Lys Lys Arg Ala Glu Lys Gln Lys Arg Lys Glu 790 795 800 atg gaa gcc aaa aat aaa gaa aat gga aaa gtt gag aat ggg tta ggc 2805 Met Glu Ala Lys Asn Lys Glu Asn Gly Lys Val Glu Asn Gly Leu Gly 805 810 815 820 aaa act gat agg aaa aaa aga att gtg aag ttt gag ccc caa gta gat 2853 Lys Thr Asp Arg Lys Lys Arg Ile Val Lys Phe Glu Pro Gln Val Asp 825 830 835 aca gaa gct gaa gac atg att agt gct gtg aag agc aga agg ttg ctt 2901 Thr Glu Ala Glu Asp Met Ile Ser Ala Val Lys Ser Arg Arg Leu Leu 840 845 850 gcc att caa gct aag aag gaa cgg gaa atc cag gaa aga gaa atg aaa 2949 Ala Ile Gln Ala Lys Lys Glu Arg Glu Ile Gln Glu Arg Glu Met Lys 855 860 865 gtg aaa ctg gaa cgc caa gct gaa gaa gaa cga ata cgg aag cac aaa 2997 Val Lys Leu Glu Arg Gln Ala Glu Glu Glu Arg Ile Arg Lys His Lys 870 875 880 gca gct gct gag aaa gct ttc cag gaa ggg att gcc aag gcc aaa cta 3045 Ala Ala Ala Glu Lys Ala Phe Gln Glu Gly Ile Ala Lys Ala Lys Leu 885 890 895 900 gtc atg cgc agg act cct att ggc aca gat cga aac cat aat aga tac 3093 Val Met Arg Arg Thr Pro Ile Gly Thr Asp Arg Asn His Asn Arg Tyr 905 910 915 tgg ctc ttc tca gat gaa gtt cca gga tta ttc att gaa aaa ggc tgg 3141 Trp Leu Phe Ser Asp Glu Val Pro Gly Leu Phe Ile Glu Lys Gly Trp 920 925 930 gta cat gac agc att gac tac cga ttc aac cat cac tgc aaa gac cac 3189 Val His Asp Ser Ile Asp Tyr Arg Phe Asn His His Cys Lys Asp His 935 940 945 aca gtc tct ggt gat gag gat tac tgt cct cgc agt aag aaa gca aac 3237 Thr Val Ser Gly Asp Glu Asp Tyr Cys Pro Arg Ser Lys Lys Ala Asn 950 955 960 tta ggt aaa aat gca agc atg aac aca caa cat gga aca gca aca gaa 3285 Leu Gly Lys Asn Ala Ser Met Asn Thr Gln His Gly Thr Ala Thr Glu 965 970 975 980 gtt gct gta gag aca acc aca ccc aaa caa gga cag aac cta tgg ttt 3333 Val Ala Val Glu Thr Thr Thr Pro Lys Gln Gly Gln Asn Leu Trp Phe 985 990 995 tta tgt gat agt caa aag gag ctg gat gag ttg cta aac tgt ctt cac 3381 Leu Cys Asp Ser Gln Lys Glu Leu Asp Glu Leu Leu Asn Cys Leu His 1000 1005 1010 cct cag gga ata aga gaa agt caa ctt aaa gag aga cta gag aag agg 3429 Pro Gln Gly Ile Arg Glu Ser Gln Leu Lys Glu Arg Leu Glu Lys Arg 1015 1020 1025 tac cag gac att att cac tct att cat cta gca cgg aag cca aat ttg 3477 Tyr Gln Asp Ile Ile His Ser Ile His Leu Ala Arg Lys Pro Asn Leu 1030 1035 1040 ggt cta aaa tct tgt gat ggc aac cag gag ctt tta aac ttc ctt cgt 3525 Gly Leu Lys Ser Cys Asp Gly Asn Gln Glu Leu Leu Asn Phe Leu Arg 1045 1050 1055 1060 agt gat ctc att gaa gtt gca aca agg tta caa aaa gga gga ctt gga 3573 Ser Asp Leu Ile Glu Val Ala Thr Arg Leu Gln Lys Gly Gly Leu Gly 1065 1070 1075 tat gtg gaa gaa aca tca gaa ttt gaa gcc cgg gtc att tca tta gag 3621 Tyr Val Glu Glu Thr Ser Glu Phe Glu Ala Arg Val Ile Ser Leu Glu 1080 1085 1090 aaa ttg aag gat ttt ggt gag tgt gtg att gcc ctt cag gcc agt gtc 3669 Lys Leu Lys Asp Phe Gly Glu Cys Val Ile Ala Leu Gln Ala Ser Val 1095 1100 1105 ata aag aaa ttt ctc caa ggc ttc atg gct ccc aag caa aag aga aga 3717 Ile Lys Lys Phe Leu Gln Gly Phe Met Ala Pro Lys Gln Lys Arg Arg 1110 1115 1120 aaa ctc caa agt gaa gat tca gca aaa act gag gaa gtg gat gaa gag 3765 Lys Leu Gln Ser Glu Asp Ser Ala Lys Thr Glu Glu Val Asp Glu Glu 1125 1130 1135 1140 aag aaa atg gta gag gaa gca aag gtt gca tct gca ctg gag aaa tgg 3813 Lys Lys Met Val Glu Glu Ala Lys Val Ala Ser Ala Leu Glu Lys Trp 1145 1150 1155 aag aca gca atc cgg gaa gct cag act ttc tcc agg atg cac gtg ctg 3861 Lys Thr Ala Ile Arg Glu Ala Gln Thr Phe Ser Arg Met His Val Leu 1160 1165 1170 ctt ggg atg ctt gat gcc tgt atc aag tgg gat atg tcc gca gaa aat 3909 Leu Gly Met Leu Asp Ala Cys Ile Lys Trp Asp Met Ser Ala Glu Asn 1175 1180 1185 gct agg tgc aaa gtt tgt cca aag aaa ggt gag gat gac aaa ttg atc 3957 Ala Arg Cys Lys Val Cys Pro Lys Lys Gly Glu Asp Asp Lys Leu Ile 1190 1195 1200 ttg tgt gat gag tgt aat aaa gcc ttc cac ctg ttt tgt ctg agg ccg 4005 Leu Cys Asp Glu Cys Asn Lys Ala Phe His Leu Phe Cys Leu Arg Pro 1205 1210 1215 1220 gcc ctc tat gaa gta cca gat ggt gag tgg cag tgc cca gct tgc cag 4053 Ala Leu Tyr Glu Val Pro Asp Gly Glu Trp Gln Cys Pro Ala Cys Gln 1225 1230 1235 ccc gct act gcc agg cgc aac tcc cgt ggc agg aac tat act gaa gag 4101 Pro Ala Thr Ala Arg Arg Asn Ser Arg Gly Arg Asn Tyr Thr Glu Glu 1240 1245 1250 tct gct tct gag gac agt gaa gat gat gag agt gat gaa gag gag gag 4149 Ser Ala Ser Glu Asp Ser Glu Asp Asp Glu Ser Asp Glu Glu Glu Glu 1255 1260 1265 gag gaa gaa gag gag gag gag gaa gaa gat tat gag gtg gct ggt ttg 4197 Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Tyr Glu Val Ala Gly Leu 1270 1275 1280 cga ttg aga cct cga aag acc atc cgg ggc aag cac agc gtc atc ccc 4245 Arg Leu Arg Pro Arg Lys Thr Ile Arg Gly Lys His Ser Val Ile Pro 1285 1290 1295 1300 cct gca gca agg tca ggc cgg cgc ccg ggt aag aag cca cac tct acc 4293 Pro Ala Ala Arg Ser Gly Arg Arg Pro Gly Lys Lys Pro His Ser Thr 1305 1310 1315 agg agg tct cag ccc aag gca cca cct gtg gat gat gct gag gtg gat 4341 Arg Arg Ser Gln Pro Lys Ala Pro Pro Val Asp Asp Ala Glu Val Asp 1320 1325 1330 gag ctg gtg ctt cag acc aag cgg agc tcc cgg agg caa agc ctg gag 4389 Glu Leu Val Leu Gln Thr Lys Arg Ser Ser Arg Arg Gln Ser Leu Glu 1335 1340 1345 ctg cag aag tgt gaa gag atc ctc cac aag atc gtg aag tac cgc ttc 4437 Leu Gln Lys Cys Glu Glu Ile Leu His Lys Ile Val Lys Tyr Arg Phe 1350 1355 1360 agc tgg ccc ttc agg gag cct gtg acc aga gat gag gcc gag gac tac 4485 Ser Trp Pro Phe Arg Glu Pro Val Thr Arg Asp Glu Ala Glu Asp Tyr 1365 1370 1375 1380 tat gat gtg atc acg cac ccc atg gac ttt cag aca gtg cag aac aaa 4533 Tyr Asp Val Ile Thr His Pro Met Asp Phe Gln Thr Val Gln Asn Lys 1385 1390 1395 tgt tcc tgt ggg agc tac cgc tct gtg cag gag ttt ctt act gac atg 4581 Cys Ser Cys Gly Ser Tyr Arg Ser Val Gln Glu Phe Leu Thr Asp Met 1400 1405 1410 aag caa gtg ttt acc aat gct gag gtt tac aac tgc cgt ggc agc cat 4629 Lys Gln Val Phe Thr Asn Ala Glu Val Tyr Asn Cys Arg Gly Ser His 1415 1420 1425 gtg cta agc tgc atg gtg aag aca gaa cag tgt cta gtg gtt ctg ttg 4677 Val Leu Ser Cys Met Val Lys Thr Glu Gln Cys Leu Val Val Leu Leu 1430 1435 1440 cat aaa cac ctt cct ggc cac cca tat gtc cgc agg aag cgc aag aag 4725 His Lys His Leu Pro Gly His Pro Tyr Val Arg Arg Lys Arg Lys Lys 1445 1450 1455 1460 ttt cct gat agg ctt gct gaa gat gaa ggg gac agt gag cca gag gcc 4773 Phe Pro Asp Arg Leu Ala Glu Asp Glu Gly Asp Ser Glu Pro Glu Ala 1465 1470 1475 gtt gga cag tcc agg gac gaa gac aga aga agt aga gag gcg gag att 4821 Val Gly Gln Ser Arg Asp Glu Asp Arg Arg Ser Arg Glu Ala Glu Ile 1480 1485 1490 cag gaa tgg ctc cag gac acg tcc ctt tac tct gcc aag atc aac tca 4869 Gln Glu Trp Leu Gln Asp Thr Ser Leu Tyr Ser Ala Lys Ile Asn Ser 1495 1500 1505 aaa gac cac aac tgt ttc atg atg ctg gtg aat aca caa ttc tgt atg 4917 Lys Asp His Asn Cys Phe Met Met Leu Val Asn Thr Gln Phe Cys Met 1510 1515 1520 gca ctc act gat act gtc acc tgagaggaag acgggggaag agacagagta 4968 Ala Leu Thr Asp Thr Val Thr 1525 1530 tgggcttaaa gaaacaagac tgtataataa atacagatta aaaaagaaaa atcgccacca 5028 tctcccctgt tggcctgatt accccgatcc tgctatgtaa cacagcaatc cctcccctgg 5088 agaccagagg ggcttggcac tgtggtggaa gccagaacga gcaggccctt aggaaagaag 5148 gcaggaacag gaactggctt caccagaaaa gctagaccct cggactcctc ctggaaactc 5208 tcagaaggga gggttatggc cctctttgtc ccttcatatt tctggacaaa gaccaccaac 5268 ccaatatcaa gccccataaa gagcttttag aaaaacagca taagcttggg atgacaggcg 5328 tttctggact ccctgtgatc tcttccaggt tcttggtctt cctcgctcgc ctccctccca 5388 ccctccctag ctgtcccccc acctcagctc ccttaccacg gccctgcctc tctacttctt 5448 ctgtcttcgt cccctggact gtccaacggc ctctggctca ctgtcccttc atcttcagca 5508 acctatcagg aaacttcttg cgcttcctgc ggacatatgg gtggccagga agtgtttatg 5568 caaca 5573 31 22 DNA Artificial Sequence Synthetically generated primer 31 tggatgatgc tgaggtggat ga 22 32 22 DNA Artificial Sequence Synthetically generated primer 32 ggggtgcgtg atgacatcat ag 22 33 24 DNA Artificial Sequence Synthetically generated primer 33 gagtgcagat aagggtggct tttt 24 34 24 DNA Artificial Sequence Synthetically generated primer 34 ccaattcacc atagtcttcg gcta 24 35 22 DNA Artificial Sequence Synthetically generated primer 35 gaaacgggag gagctgaaaa ag 22 36 22 DNA Artificial Sequence Synthetically generated primer 36 ccttcagggg tatccaccaa tc 22 37 5 PRT Homo sapiens VARIANT (1)...(5) Xaa = Any Amino Acid 37 Leu Xaa Xaa Leu Leu 1 5 38 59 PRT Homo sapiens 38 Ser Trp Pro Phe Leu Lys Leu Val Ser Lys Ile Gln Val Pro Asp Tyr 1 5 10 15 Tyr Asp Ile Ile Lys Lys Pro Ile Ala Leu Asn Ile Ile Arg Glu Lys 20 25 30 Val Asn Lys Cys Glu Tyr Lys Leu Ala Ser Glu Phe Ile Asp Asp Ile 35 40 45 Glu Leu Met Phe Ser Asn Cys Phe Glu Tyr Asn 50 55 39 59 PRT Saccharomyces cerevisiae 39 Ser Trp Pro Phe Leu Lys Pro Val Asn Lys Lys Gln Val Lys Asp Tyr 1 5 10 15 Tyr Thr Val Ile Lys Arg Pro Met Asp Ile Glu Ile Ile Gly Lys Asn 20 25 30 Ile Glu Ala His Arg Tyr His Ser Arg Ala Glu Tyr Leu Ala Asp Ile 35 40 45 Glu Leu Ile Ala Thr Asn Cys Glu Gln Tyr Asn 50 55 40 59 PRT Homo sapiens 40 Thr Tyr Pro Phe His Thr Pro Val Asn Ala Lys Val Val Lys Asp Tyr 1 5 10 15 Tyr Lys Ile Ile Thr Arg Pro Met Asp Leu Gln Ile Leu Arg Glu Asn 20 25 30 Val Arg Lys Arg Leu Tyr Pro Ser Arg Glu Glu Phe Arg Glu His Leu 35 40 45 Glu Leu Ile Val Lys Asn Ser Ala Thr Tyr Asn 50 55 41 59 PRT Homo sapiens 41 Ala Trp Pro Phe Met Glu Pro Val Lys Arg Thr Glu Ala Pro Gly Tyr 1 5 10 15 Tyr Glu Val Ile Arg Ser Pro Met Asp Leu Lys Ile Met Ser Glu Arg 20 25 30 Leu Lys Asn Arg Tyr Tyr Val Ser Lys Lys Leu Phe Met Ala Asp Leu 35 40 45 Gln Arg Val Phe Thr Asn Cys Lys Glu Tyr Asn 50 55 42 61 PRT Homo sapiens 42 Ser Leu Pro Phe Arg Gln Pro Val Asp Pro Gln Leu Leu Gly Ile Pro 1 5 10 15 Asp Tyr Glu Asp Ile Val Lys Asn Pro Met Asp Leu Ser Ile Ile Lys 20 25 30 Arg Lys Leu Asp Thr Gly Gln Tyr Gln Glu Pro Trp Gln Tyr Val Asp 35 40 45 Asp Val Trp Leu Met Phe Asn Asn Ala Trp Leu Tyr Asn 50 55 60 43 45 PRT Homo sapiens 43 Cys Lys Ile Cys Arg Lys Lys Gly Asp Ala Glu Asn Met Val Leu Cys 1 5 10 15 Asp Gly Cys Asp Arg Gly His His Thr Tyr Cys Val Arg Pro Lys Leu 20 25 30 Lys Thr Val Pro Glu Gly Asp Trp Phe Cys Pro Glu Cys 35 40 45 44 44 PRT Caenorhabditis elegans 44 Cys Gln Ile Cys Lys Ser Met Asp Gly Asp Glu Met Leu Val Cys Asp 1 5 10 15 Gly Cys Glu Ser Gly Cys His Met Glu Cys Phe Arg Pro Arg Met Thr 20 25 30 Lys Val Pro Glu Gly Asp Trp Phe Cys Gln Arg Cys 35 40 45 45 PRT Homo sapiens 45 Cys Met Phe Cys Gly Arg Gly Asn Asn Glu Asp Lys Leu Leu Leu Cys 1 5 10 15 Asp Gly Cys Asp Asp Ser Tyr His Thr Phe Cys Glu Ile Pro Pro Leu 20 25 30 Pro Asp Val Pro Lys Gly Asp Trp Arg Cys Pro Lys Cys 35 40 45 46 54 PRT Homo sapiens 46 Cys Met Phe Cys Leu Gly Thr Lys Glu Gln Asn Arg Glu Lys Lys Pro 1 5 10 15 Glu Glu Leu Ile Ser Cys Ala Asp Cys Gly Asn Ser Gly His Pro Ser 20 25 30 Cys Leu Lys Phe Ser Pro Glu Leu Thr Val Arg Val Lys Ala Leu Arg 35 40 45 Trp Gln Cys Ile Glu Cys 50 47 46 PRT Homo sapiens 47 Cys Ser Ser Cys Arg Asp Gln Gly Lys Asn Ala Asp Asn Met Leu Phe 1 5 10 15 Cys Asp Ser Cys Asp Arg Gly Phe His Met Glu Cys Cys Asp Pro Pro 20 25 30 Leu Thr Arg Met Pro Lys Gly Met Trp Ile Cys Gln Ile Cys 35 40 45 48 75 PRT Homo sapiens 48 Cys Glu Lys Cys Phe Asn Glu Ile Gln Gly Glu Ser Val Ser Leu Gly 1 5 10 15 Asp Asp Pro Ser Gln Pro Gln Thr Thr Ile Asn Asn Glu Gln Phe Ser 20 25 30 Lys Arg Lys Asn Asp Thr Leu Asp Pro Glu Leu Phe Val Glu Cys Thr 35 40 45 Glu Cys Gly Arg Lys Met His Gln Ile Cys Val Leu His His Glu Ile 50 55 60 Ile Trp Pro Ala Gly Phe Val Cys Asp Gly Cys 65 70 75 49 75 PRT Homo sapiens 49 Cys Glu Lys Cys Phe Thr Glu Ile Gln Gly Glu Asn Val Thr Leu Gly 1 5 10 15 Asp Asp Pro Ser Gln Pro Gln Thr Thr Ile Ser Lys Asp Gln Phe Glu 20 25 30 Lys Lys Lys Asn Asp Thr Leu Asp Pro Glu Pro Phe Val Asp Cys Lys 35 40 45 Glu Cys Gly Arg Lys Met His Gln Ile Cys Val Leu His Tyr Asp Ile 50 55 60 Ile Trp Pro Ser Gly Phe Val Cys Asp Asn Cys 65 70 75 50 59 PRT Homo sapiens 50 Ser Trp Pro Phe Leu Lys Leu Val Ser Lys Ile Gln Val Pro Asp Tyr 1 5 10 15 Tyr Asp Ile Ile Lys Lys Pro Ile Ala Leu Asn Ile Ile Arg Glu Lys 20 25 30 Val Asn Lys Cys Glu Tyr Lys Leu Ala Ser Glu Phe Ile Asp Asp Ile 35 40 45 Glu Leu Met Phe Ser Asn Cys Phe Glu Tyr Asn 50 55 51 59 PRT Homo sapiens 51 Ser Trp Pro Phe His His Pro Val Asn Lys Lys Phe Val Pro Asp Tyr 1 5 10 15 Tyr Lys Val Ile Val Asn Pro Met Asp Ile Glu Thr Ile Arg Lys Asn 20 25 30 Ile Ser Lys His Lys Tyr Gln Ser Arg Glu Ser Phe Leu Asp Asp Val 35 40 45 Asn Leu Ile Leu Ala Asn Ser Val Lys Tyr Asn 50 55 52 59 PRT Homo sapiens 52 Ala Trp Pro Phe Leu Glu Pro Val Asn Pro Arg Leu Val Ser Gly Tyr 1 5 10 15 Arg Arg Ile Ile Lys Asn Pro Met Asp Phe Ser Thr Met Arg Glu Arg 20 25 30 Leu Leu Arg Gly Gly Tyr Thr Ser Ser Glu Glu Phe Ala Ala Asp Ala 35 40 45 Leu Leu Val Phe Asp Asn Cys Gln Thr Phe Asn 50 55 53 59 PRT Homo sapiens 53 Ala Trp Pro Phe Met Glu Pro Val Lys Arg Thr Glu Ala Pro Gly Tyr 1 5 10 15 Tyr Glu Val Ile Arg Ser Pro Met Asp Leu Lys Thr Met Ser Glu Arg 20 25 30 Leu Lys Asn Arg Tyr Tyr Val Ser Lys Lys Leu Phe Met Ala Asp Leu 35 40 45 Gln Arg Val Phe Thr Asn Cys Lys Glu Tyr Asn 50 55 54 82 PRT Caenorhabditis elegans 54 Ala Leu Pro Phe Leu Glu Pro Val Asn Pro Lys Leu Val Pro Gly Tyr 1 5 10 15 Lys Met Ile Ile Ser Lys Pro Met Asp Leu Lys Thr Ile Arg Gln Lys 20 25 30 Asn Glu Lys Leu Ile Val Ser Glu Thr Tyr Gln Phe Cys Phe Phe Ala 35 40 45 Ile Phe Asp Leu Lys Leu Lys Met Lys Ile Thr Gln Tyr Glu Thr Pro 50 55 60 Glu Asp Phe Ala Glu Asp Ile Glu Leu Met Phe Ala Asn Cys Arg Gln 65 70 75 80 Phe Asn 55 61 PRT Homo sapiens 55 Ser Leu Pro Phe Arg Gln Pro Val Asp Pro Gln Leu Leu Gly Ile Pro 1 5 10 15 Asp Tyr Phe Asp Ile Val Lys Met Pro Met Asp Leu Ser Thr Ile Lys 20 25 30 Arg Lys Leu Asp Thr Gly Gln Tyr Gln Glu Pro Trp Gln Tyr Val Asp 35 40 45 Asp Val Trp Leu Met Phe Asn Asn Ala Trp Leu Tyr Asn 50 55 60 56 45 PRT Homo sapiens 56 Cys Lys Ile Cys Arg Lys Lys Gly Asp Ala Glu Asn Met Val Leu Cys 1 5 10 15 Asp Gly Cys Asp Arg Gly His His Thr Tyr Cys Val Arg Pro Lys Leu 20 25 30 Lys Thr Val Pro Glu Gly Asp Trp Phe Cys Pro Glu Cys 35 40 45 57 44 PRT Caenorhabditis elegans 57 Cys Gln Ile Cys Lys Ser Met Asp Gly Asp Glu Met Leu Val Cys Asp 1 5 10 15 Gly Cys Glu Ser Gly Cys His Met Glu Cys Phe Arg Pro Arg Met Thr 20 25 30 Lys Val Pro Glu Gly Asp Trp Phe Cys Gln Arg Cys 35 40 58 44 PRT Homo sapiens 58 Cys Met Phe Cys Gly Arg Gly Asn Asn Glu Asp Lys Leu Leu Leu Cys 1 5 10 15 Asp Gly Cys Asp Ser Tyr His Thr Phe Cys Leu Ile Pro Pro Leu Pro 20 25 30 Asp Val Pro Lys Gly Asp Trp Arg Cys Pro Lys Cys 35 40 59 54 PRT Homo sapiens 59 Cys Ser Phe Cys Leu Gly Thr Lys Glu Gln Asn Arg Glu Lys Lys Pro 1 5 10 15 Glu Glu Leu Ile Ser Cys Ala Asp Cys Gly Asn Ser Gly His Pro Ser 20 25 30 Cys Leu Lys Phe Ser Pro Glu Leu Thr Val Arg Val Lys Ala Leu Arg 35 40 45 Trp Gln Cys Ile Glu Cys 50 60 46 PRT Homo sapiens 60 Cys Ser Ser Cys Arg Asp Gln Gly Lys Asn Ala Asp Asn Met Leu Phe 1 5 10 15 Cys Asp Ser Cys Asp Arg Gly Phe His Met Glu Cys Cys Asp Pro Pro 20 25 30 Leu Thr Arg Met Pro Lys Gly Met Trp Ile Cys Gln Ile Cys 35 40 45 61 75 PRT Homo sapiens 61 Cys Glu Lys Cys Phe Asn Glu Ile Gln Gly Glu Ser Val Ser Leu Gly 1 5 10 15 Asp Asp Pro Ser Gln Pro Gln Thr Thr Ile Asn Lys Glu Gln Phe Ser 20 25 30 Lys Arg Lys Asn Asp Thr Leu Asp Pro Glu Leu Phe Val Glu Cys Thr 35 40 45 Glu Cys Gly Arg Lys Met His Gln Ile Cys Val Leu His His Glu Ile 50 55 60 Ile Trp Pro Ala Gly Phe Val Cys Asp Gly Cys 65 70 75 62 45 PRT Homo sapiens 62 Cys Leu Val Cys Arg Lys Gly Asp Asn Asp Arg Phe Leu Leu Leu Cys 1 5 10 15 Asp Gly Cys Asp Arg Gly Cys His Ile Tyr Cys His Arg Pro Lys Met 20 25 30 Glu Ala Val Pro Glu Gly Asp Trp Phe Cys Thr Val Cys 35 40 45 63 211 PRT Homo sapiens 63 Arg Glu Glu Lys Arg Lys Tyr Val Glu Tyr Leu Lys Gln Trp Ser Lys 1 5 10 15 Pro Arg Glu Asp Met Glu Cys Asp Asp Leu Lys Glu Leu Pro Glu Pro 20 25 30 Thr Pro Val Lys Thr Arg Leu Pro Pro Glu Ile Phe Gly Asp Ala Leu 35 40 45 Met Val Leu Glu Phe Leu Asn Ala Phe Gly Glu Leu Phe Asp Leu Gln 50 55 60 Asp Glu Phe Pro Asp Gly Val Thr Leu Glu Val Leu Glu Glu Ala Leu 65 70 75 80 Val Gly Asn Asp Ser Glu Gly Pro Leu Cys Glu Leu Leu Phe Phe Phe 85 90 95 Leu Thr Ala Ile Phe Gln Ala Ile Ala Glu Glu Glu Glu Glu Val Ala 100 105 110 Lys Glu Gln Leu Thr Asp Ala Asp Thr Lys Gly Cys Ser Leu Lys Ser 115 120 125 Leu Asp Leu Asp Ser Cys Thr Leu Ser Glu Ile Leu Arg Leu His Ile 130 135 140 Leu Ala Ser Gly Ala Asp Val Thr Ser Ala Asn Ala Lys Tyr Arg Tyr 145 150 155 160 Gln Lys Arg Gly Gly Phe Asp Ala Thr Asp Asp Ala Cys Met Glu Leu 165 170 175 Arg Leu Ser Asn Pro Ser Leu Val Lys Lys Leu Ser Ser Thr Ser Val 180 185 190 Tyr Asp Leu Thr Pro Gly Glu Lys Met Lys Ile Leu His Ala Leu Cys 195 200 205 Gly Lys Leu 210 64 185 PRT Caenorhabditis elegans 64 Leu Asn Asp Glu Phe Thr Glu Glu Leu Val His Ser Gln Ile Met Ser 1 5 10 15 Asn Gly Val Asp Glu Cys Lys Ile Arg Glu Arg Glu Ala Asp Asp Leu 20 25 30 Leu Val Asn Ile Asn Asp Val Arg His Leu Pro Asp Phe Ser Arg Ile 35 40 45 Gly Asn Gln Cys Leu Ser Ser Gln Gly Phe Ala Asp Ala Leu Met Val 50 55 60 His Glu Phe Val Gln Asn Phe Gly His Val Leu Gly Ile Asp Leu Glu 65 70 75 80 Ile Ala Pro Lys Leu Glu Ser Leu Cys Ala Gly Leu Asp Gly Asp Ala 85 90 95 Asn His Ala Glu Gln Thr Leu Gln Leu Thr Arg Gln Leu Leu Arg Leu 100 105 110 Ala Leu Glu Phe Pro Gly Met Gly Asn Glu Lys Arg Phe Gly Gln Gly 115 120 125 Gly Gly Glu Met Gly Leu Asp Arg Glu Asn Phe Ser Glu Val Met Arg 130 135 140 Leu Phe Leu Ile Asp Lys Gly Lys Arg Gly Glu Glu Leu Ser Gln Pro 145 150 155 160 Leu Leu Thr Cys Asn Phe Leu Ser Ile Ser Pro Glu Gln Lys Ala Ser 165 170 175 Ile Leu Ala Phe Leu Cys Asp Glu Leu 180 185 65 175 PRT Homo sapiens 65 Leu Glu Glu Arg Gln Lys Gln Gln Met Ile Leu Glu Glu Met Lys Lys 1 5 10 15 Pro Thr Glu Asp Met Cys Leu Thr Asp His Gln Pro Leu Pro Asp Phe 20 25 30 Ser Arg Val Pro Gly Leu Thr Leu Pro Ser Gly Ala Phe Ser Asp Cys 35 40 45 Leu Thr Ile Val Glu Phe Leu His Ser Phe Gly Lys Val Leu Gly Phe 50 55 60 Asp Pro Ala Lys Asp Val Pro Ser Leu Gly Val Leu Gln Glu Gly Leu 65 70 75 80 Leu Cys Gln Gly Asp Ser Leu Gly Glu Val Gln Asp Leu Leu Val Arg 85 90 95 Leu Leu Lys Ala Ala Leu His Asp Pro Gly Phe Pro Ser Tyr Cys Gln 100 105 110 Ser Leu Lys Ile Leu Gly Glu Lys Val Ser Glu Ile Pro Leu Thr Arg 115 120 125 Asp Asn Val Ser Glu Ile Leu Arg Cys Pro Leu Met Ala Tyr Gly Val 130 135 140 Glu Pro Ala Leu Cys Asp Arg Leu Arg Thr Gln Pro Pro Gln Ala Gln 145 150 155 160 Pro Pro Gln Lys Ala Ala Val Leu Ala Phe Pro Val His Glu Leu 165 170 175 66 176 PRT Homo sapiens 66 Leu Glu Gln Arg Arg Leu Glu Leu Glu Met Ala Lys Glu Leu Lys Lys 1 5 10 15 Pro Asn Glu Asp Met Cys Leu Ala Asp Gln Lys Pro Leu Pro Glu Leu 20 25 30 Pro Arg Ile Pro Gly Leu Val Leu Ser Gly Ser Thr Phe Ser Asp Cys 35 40 45 Leu Met Val Val Gln Phe Leu Arg Asn Phe Gly Lys Val Leu Gly Phe 50 55 60 Asp Val Asn Ile Asp Val Pro Asn Leu Ser Val Leu Gln Glu Gly Leu 65 70 75 80 Leu Asn Ile Gly Asp Ser Met Gly Glu Val Gln Asp Leu Leu Val Arg 85 90 95 Leu Leu Ser Ala Ala Val Cys Asp Pro Gly Leu Ile Thr Gly Tyr Lys 100 105 110 Ala Lys Thr Ala Leu Gly Glu His Leu Leu Asn Val Gly Val Asn Arg 115 120 125 Asp Asn Val Ser Glu Ile Leu Gln Ile Phe Met Glu Ala His Cys Gly 130 135 140 Gln Thr Glu Leu Thr Glu Ser Leu Lys Thr Lys Ala Phe Gln Ala His 145 150 155 160 Thr Pro Ala Gln Lys Ala Ser Val Leu Ala Phe Leu Ile Asn Glu Leu 165 170 175 67 59 PRT Homo sapiens 67 Tyr Pro Ile Thr Ala Val Ser Leu Met Glu Ala Leu Ser Ala Asp Lys 1 5 10 15 Gly Gly Phe Leu Tyr Leu Asn Arg Val Leu Val Ile Leu Leu Gln Thr 20 25 30 Leu Leu Gln Asp Glu Ile Ala Glu Asp Tyr Gly Glu Leu Gly Met Lys 35 40 45 Leu Ser Glu Ile Pro Leu His Ser Val Ser Glu 50 55 68 65 PRT Homo sapiens 68 Tyr Pro Ile Thr Ala Val Ser Leu Met Glu Ala Leu Ser Ala Asp Lys 1 5 10 15 Gly Gly Phe Leu Tyr Leu Asn Arg Val Leu Val Ile Leu Leu Gln Thr 20 25 30 Leu Leu Gln Thr Leu Leu Gln Asp Glu Ile Ala Glu Asp Tyr Gly Glu 35 40 45 Leu Gly Met Lys Leu Ser Lys Ile Pro Leu Thr Leu His Ser Val Ser 50 55 60 Glu 65 69 1525 PRT Homo sapiens 69 Met Ala Pro Leu Leu Gly Arg Lys Pro Phe Pro Leu Val Asn Pro Leu 1 5 10 15 Pro Gly Glu Glu Pro Phe Phe Thr Ile Pro His Thr Gln Glu Ala Phe 20 25 30 Arg Thr Arg Glu Glu Tyr Glu Ala Arg Leu Glu Arg Tyr Ser Glu Arg 35 40 45 Ile Trp Thr Cys Lys Ser Thr Gly Ser Ser Gln Leu Thr His Lys Glu 50 55 60 Ala Trp Glu Glu Glu Gln Glu Val Ala Glu Leu Leu Lys Glu Glu Phe 65 70 75 80 Pro Ala Trp Tyr Glu Lys Leu Val Leu Glu Met Val His His Asn Thr 85 90 95 Ala Ser Leu Glu Lys Leu Val Asp Thr Ala Trp Leu Glu Ile Met Thr 100 105 110 Lys Tyr Ala Val Gly Glu Glu Cys Asp Phe Glu Val Gly Lys Glu Lys 115 120 125 Met Leu Lys Val Lys Ile Val Lys Ile His Pro Leu Glu Lys Val Asp 130 135 140 Glu Glu Ala Thr Glu Lys Lys Ser Asp Gly Ala Cys Asp Ser Pro Ser 145 150 155 160 Ser Asp Lys Glu Asn Ser Ser Gln Ile Ala Gln Asp His Gln Lys Lys 165 170 175 Glu Thr Val Val Lys Glu Asp Glu Gly Arg Arg Glu Ser Ile Asn Asp 180 185 190 Arg Ala Arg Arg Ser Pro Arg Lys Leu Pro Thr Ser Leu Lys Lys Gly 195 200 205 Glu Arg Lys Trp Ala Pro Pro Lys Phe Leu Pro His Lys Tyr Asp Val 210 215 220 Lys Leu Gln Asn Glu Asp Lys Ile Ile Ser Asn Val Pro Ala Asp Ser 225 230 235 240 Leu Ile Arg Thr Glu Arg Pro Pro Asn Lys Glu Ile Val Arg Tyr Phe 245 250 255 Ile Arg His Asn Ala Leu Arg Ala Gly Thr Gly Glu Asn Ala Pro Trp 260 265 270 Val Val Glu Asp Glu Leu Val Lys Lys Tyr Ser Leu Pro Ser Lys Phe 275 280 285 Ser Asp Phe Leu Leu Asp Pro Tyr Lys Tyr Met Thr Leu Asn Pro Ser 290 295 300 Thr Lys Arg Lys Asn Thr Gly Ser Pro Asp Arg Lys Pro Ser Lys Lys 305 310 315 320 Ser Lys Thr Asp Asn Ser Ser Leu Ser Ser Pro Leu Asn Pro Lys Leu 325 330 335 Trp Cys His Val His Leu Lys Lys Ser Leu Ser Gly Ser Pro Leu Lys 340 345 350 Val Lys Asn Ser Lys Asn Ser Lys Ser Pro Glu Glu His Leu Glu Glu 355 360 365 Met Met Lys Met Met Ser Pro Asn Lys Leu His Thr Asn Pro His Ile 370 375 380 Pro Lys Lys Gly Pro Pro Ala Lys Lys Pro Gly Lys His Ser Asp Lys 385 390 395 400 Pro Leu Lys Ala Lys Gly Arg Ser Lys Gly Ile Leu Asn Gly Gln Lys 405 410 415 Ser Thr Gly Asn Ser Lys Ser Pro Lys Lys Gly Leu Lys Thr Pro Lys 420 425 430 Thr Lys Met Lys Gln Met Thr Leu Leu Asp Met Ala Lys Gly Thr Gln 435 440 445 Lys Met Thr Arg Ala Pro Arg Asn Ser Gly Gly Thr Pro Arg Thr Ser 450 455 460 Ser Lys Pro His Lys His Leu Pro Pro Ala Ala Leu His Leu Ile Ala 465 470 475 480 Tyr Tyr Lys Glu Asn Lys Asp Arg Glu Asp Lys Arg Ser Ala Leu Ser 485 490 495 Cys Val Ile Ser Lys Thr Ala Arg Leu Leu Ser Ser Glu Asp Arg Ala 500 505 510 Arg Leu Pro Glu Glu Leu Arg Ser Leu Val Gln Lys Arg Tyr Glu Leu 515 520 525 Leu Glu His Lys Lys Arg Trp Ala Ser Met Ser Glu Glu Gln Arg Lys 530 535 540 Glu Tyr Leu Lys Lys Lys Arg Glu Glu Leu Lys Lys Lys Leu Lys Glu 545 550 555 560 Lys Ala Lys Glu Arg Arg Glu Lys Glu Met Leu Glu Arg Leu Glu Lys 565 570 575 Gln Lys Arg Tyr Glu Asp Gln Glu Leu Thr Gly Lys Asn Leu Pro Ala 580 585 590 Phe Arg Leu Val Asp Thr Pro Glu Gly Leu Pro Asn Thr Leu Phe Gly 595 600 605 Asp Val Ala Met Val Val Glu Phe Leu Ser Cys Tyr Ser Gly Leu Leu 610 615 620 Leu Pro Asp Ala Gln Tyr Pro Ile Thr Ala Val Ser Leu Met Glu Ala 625 630 635 640 Leu Ala Asp Lys Gly Gly Phe Leu Tyr Leu Asn Arg Val Leu Val Ile 645 650 655 Leu Leu Gln Thr Leu Leu Gln Asp Glu Ile Ala Glu Asp Tyr Gly Glu 660 665 670 Leu Gly Met Lys Leu Ser Glu Ile Pro Leu Thr Leu His Ser Val Ser 675 680 685 Glu Leu Val Arg Leu Cys Leu Arg Arg Ser Asp Val Gln Glu Glu Ser 690 695 700 Glu Gly Ser Asp Thr Asp Asp Asn Lys Asp Ser Ala Ala Phe Glu Asp 705 710 715 720 Asn Glu Val Gln Asp Glu Phe Leu Glu Lys Leu Glu Thr Ser Glu Phe 725 730 735 Phe Glu Leu Thr Ser Glu Glu Lys Leu Gln Ile Leu Thr Ala Leu Cys 740 745 750 His Arg Ile Leu Met Thr Tyr Ser Val Gln Asp His Met Glu Thr Arg 755 760 765 Gln Gln Met Ser Ala Glu Leu Trp Lys Glu Arg Leu Ala Val Leu Lys 770 775 780 Glu Glu Asn Asp Lys Lys Arg Ala Glu Lys Gln Lys Arg Lys Glu Met 785 790 795 800 Glu Ala Lys Asn Lys Glu Asn Gly Lys Val Glu Asn Gly Leu Gly Lys 805 810 815 Thr Asp Arg Lys Lys Arg Ile Val Lys Phe Glu Pro Gln Val Asp Thr 820 825 830 Glu Ala Glu Asp Met Ile Ser Ala Val Lys Ser Arg Arg Leu Leu Ala 835 840 845 Ile Gln Ala Lys Lys Glu Arg Glu Ile Gln Glu Arg Glu Met Lys Val 850 855 860 Lys Leu Glu Arg Gln Ala Glu Glu Glu Arg Ile Arg Lys His Lys Ala 865 870 875 880 Ala Ala Glu Lys Ala Phe Gln Glu Gly Ile Ala Lys Ala Lys Leu Val 885 890 895 Met Arg Arg Thr Pro Ile Gly Thr Asp Arg Asn His Asn Arg Tyr Trp 900 905 910 Leu Phe Ser Asp Glu Val Pro Gly Leu Phe Ile Glu Lys Gly Trp Val 915 920 925 His Asp Ser Ile Asp Tyr Arg Phe Asn His His Cys Lys Asp His Thr 930 935 940 Val Ser Gly Cys Glu Asp Tyr Cys Pro Arg Ser Lys Lys Ala Asn Leu 945 950 955 960 Gly Lys Asn Ala Ser Met Asn Thr Gln His Gly Thr Ala Thr Glu Val 965 970 975 Ala Val Glu Thr Thr Thr Pro Lys Gln Gly Gln Asn Leu Trp Phe Leu 980 985 990 Cys Asp Ser Gln Lys Glu Leu Asp Glu Leu Leu Asn Cys Leu His Pro 995 1000 1005 Gln Gly Ile Arg Glu Ser Gln Leu Lys Glu Arg Leu Glu Lys Arg Tyr 1010 1015 1020 Gln Asp Ile Ile His Ser Leu His Leu Ala Arg Lys Pro Asn Leu Gly 1025 1030 1035 1040 Leu Lys Ser Cys Asp Gly Asn Gln Glu Leu Leu Asn Phe Leu Arg Ser 1045 1050 1055 Asp Leu Ile Glu Val Ala Thr Arg Leu Gln Lys Gly Gly Leu Gly Tyr 1060 1065 1070 Val Glu Glu Thr Ser Glu Phe Glu Ala Arg Val Ile Ser Leu Glu Lys 1075 1080 1085 Leu Lys Asp Phe Gly Glu Cys Val Ile Ala Leu Gln Ala Ser Val Ile 1090 1095 1100 Lys Lys Phe Leu Gln Gly Phe Met Ala Pro Lys Gln Lys Arg Arg Lys 1105 1110 1115 1120 Leu Gln Ser Glu Asp Ser Ala Lys Thr Glu Glu Val Asp Glu Glu Lys 1125 1130 1135 Lys Met Val Glu Glu Ala Lys Val Ala Ser Ala Leu Glu Lys Trp Lys 1140 1145 1150 Thr Ala Ile Arg Glu Ala Gln Thr Phe Ser Arg Met His Val Leu Leu 1155 1160 1165 Gly Met Leu Asp Ala Cys Ile Lys Trp Asp Met Ser Ala Glu Asn Ala 1170 1175 1180 Arg Cys Lys Val Cys Pro Lys Lys Gly Glu Asp Asp Lys Leu Ile Leu 1185 1190 1195 1200 Cys Asp Glu Cys Asn Lys Ala Phe His Leu Phe Cys Leu Arg Pro Ala 1205 1210 1215 Leu Tyr Glu Val Pro Asp Gly Glu Trp Gln Cys Pro Ala Cys Gln Pro 1220 1225 1230 Ala Thr Ala Arg Arg Asn Ser Arg Gly Arg Asn Tyr Thr Glu Glu Ser 1235 1240 1245 Ala Ser Glu Asp Ser Glu Asp Glu Ser Asp Glu Glu Glu Glu Glu Glu 1250 1255 1260 Glu Glu Glu Glu Glu Glu Glu Asp Tyr Glu Val Ala Gly Leu Arg Leu 1265 1270 1275 1280 Arg Pro Arg Lys Thr Ile Arg Gly Lys His Ser Val Ile Pro Pro Ala 1285 1290 1295 Ala Arg Ser Gly Arg Arg Pro Gly Lys Lys Pro His Ser Thr Arg Arg 1300 1305 1310 Ser Gln Pro Lys Ala Pro Pro Val Asp Ala Glu Val Asp Glu Leu Val 1315 1320 1325 Leu Gln Thr Lys Arg Ser Ser Arg Arg Gln Ser Leu Glu Leu Gln Lys 1330 1335 1340 Cys Glu Glu Ile Leu His Lys Ile Val Lys Tyr Arg Phe Ser Trp Pro 1345 1350 1355 1360 Phe Arg Glu Pro Val Thr Arg Asp Glu Ala Glu Asp Tyr Tyr Asp Val 1365 1370 1375 Ile Thr His Pro Met Asp Phe Gln Thr Val Gln Asn Lys Cys Ser Cys 1380 1385 1390 Gly Ser Tyr Arg Ser Val Gln Glu Phe Leu Thr Asp Met Lys Gln Val 1395 1400 1405 Phe Thr Asn Ala Glu Val Tyr Asn Cys Arg Gly Ser His Val Leu Ser 1410 1415 1420 Cys Met Val Lys Thr Glu Gln Cys Leu Val Val Leu Leu His Lys His 1425 1430 1435 1440 Leu Pro Gly His Pro Tyr Val Arg Arg Lys Arg Lys Lys Phe Pro Asp 1445 1450 1455 Arg Leu Ala Glu Asp Glu Gly Asp Ser Glu Pro Glu Ala Val Gly Gln 1460 1465 1470 Ser Arg Asp Glu Asp Arg Arg Ser Arg Glu Ala Glu Ile Gln Glu Trp 1475 1480 1485 Leu Gln Asp Thr Ser Leu Tyr Ala Ser Ala Lys Ile Asn Ser Lys Asp 1490 1495 1500 His Asn Cys Phe Met Met Leu Val Asn Thr Gln Phe Cys Met Ala Leu 1505 1510 1515 1520 Thr Asp Thr Val Thr 1525 70 1673 PRT Homo sapiens 70 Met Glu Asp Ala Ser Glu Ser Ser Arg Gly Val Ala Pro Leu Ile Asn 1 5 10 15 Asn Val Val Leu Pro Gly Ser Pro Leu Ser Leu Pro Val Ser Val Thr 20 25 30 Gly Cys Lys Ser His Arg Val Ala Asn Lys Lys Val Glu Ala Arg Ser 35 40 45 Glu Lys Leu Leu Pro Thr Ala Leu Pro Pro Ser Glu Pro Lys Val Asp 50 55 60 Gln Lys Leu Pro Arg Ser Ser Glu Arg Arg Gly Ser Gly Gly Gly Thr 65 70 75 80 Gln Phe Pro Ala Arg Ser Arg Ala Val Ala Ala Gly Glu Ala Ala Ala 85 90 95 Arg Gly Ala Ala Gly Pro Glu Arg Gly Ser Pro Leu Gly Arg Arg Val 100 105 110 Ser Pro Arg Cys Leu Cys Ser Gly Glu Gly Gly Gln Val Ala Val Gly 115 120 125 Val Ile Ala Gly Lys Arg Gly Arg Arg Gly Arg Asp Gly Ser Arg Arg 130 135 140 Ala Pro Gly Gly Arg Glu Met Pro Leu Leu His Arg Lys Pro Phe Val 145 150 155 160 Arg Gln Lys Pro Pro Ala Asp Leu Arg Pro Asp Glu Glu Val Phe Tyr 165 170 175 Cys Lys Val Thr Asn Glu Ile Phe Arg His Tyr Asp Asp Phe Phe Glu 180 185 190 Arg Thr Ile Leu Cys Asn Ser Leu Val Trp Ser Cys Ala Val Thr Gly 195 200 205 Arg Pro Gly Leu Thr Tyr Gln Glu Ala Leu Glu Ser Glu Lys Lys Ala 210 215 220 Arg Gln Asn Leu Gln Ser Phe Pro Glu Pro Leu Ile Ile Pro Val Leu 225 230 235 240 Tyr Leu Thr Ser Leu Thr His Arg Ser Arg Leu His Glu Ile Cys Asp 245 250 255 Asp Ile Phe Ala Tyr Val Lys Asp Arg Tyr Phe Val Glu Glu Thr Val 260 265 270 Glu Val Ile Arg Asn Asn Gly Ala Arg Leu Gln Cys Thr Ile Leu Glu 275 280 285 Val Leu Pro Pro Ser His Gln Asn Gly Phe Ala Asn Gly His Val Asn 290 295 300 Ser Val Asp Gly Glu Thr Ile Ile Ile Ser Asp Ser Asp Asp Ser Glu 305 310 315 320 Thr Gln Ser Cys Ser Phe Gln Asn Gly Lys Lys Lys Asp Ala Ile Asp 325 330 335 Pro Leu Leu Phe Lys Tyr Lys Val Gln Pro Thr Lys Lys Glu Leu His 340 345 350 Glu Ser Ala Ile Val Lys Ala Thr Gln Ile Ser Arg Arg Lys His Leu 355 360 365 Phe Ser Arg Asp Lys Leu Lys Leu Phe Leu Lys Gln His Cys Glu Pro 370 375 380 Gln Glu Gly Val Ile Lys Ile Lys Ala Ser Ser Leu Ser Thr Tyr Lys 385 390 395 400 Ile Ala Glu Gln Asp Phe Ser Tyr Phe Phe Pro Asp Asp Pro Pro Thr 405 410 415 Phe Ile Phe Ser Pro Ala Asn Arg Arg Arg Gly Arg Pro Pro Lys Arg 420 425 430 Ile His Ile Ser Gln Glu Asp Asn Val Ala Asn Lys Gln Thr Leu Ala 435 440 445 Ser Tyr Arg Ser Lys Ala Thr Lys Glu Arg Asp Lys Leu Leu Lys Gln 450 455 460 Glu Glu Met Lys Ser Leu Ala Phe Glu Lys Ala Lys Leu Lys Arg Glu 465 470 475 480 Lys Ala Asp Ala Leu Glu Ala Lys Lys Lys Glu Lys Glu Asp Lys Glu 485 490 495 Lys Lys Arg Glu Glu Leu Lys Lys Ile Val Glu Glu Glu Arg Leu Lys 500 505 510 Lys Lys Glu Glu Lys Glu Arg Leu Lys Val Glu Arg Glu Lys Glu Arg 515 520 525 Glu Lys Leu Arg Glu Glu Lys Arg Lys Tyr Val Glu Tyr Lys Gln Trp 530 535 540 Ser Lys Pro Arg Glu Asp Met Glu Cys Asp Asp Leu Lys Glu Leu Pro 545 550 555 560 Glu Pro Thr Pro Val Lys Thr Arg Leu Pro Pro Glu Ile Phe Gly Asp 565 570 575 Ala Leu Met Val Leu Glu Phe Leu Asn Ala Phe Gly Glu Leu Phe Asp 580 585 590 Leu Gln Asp Glu Phe Pro Asp Gly Val Thr Leu Glu Val Leu Glu Glu 595 600 605 Ala Leu Val Gly Asn Asp Ser Glu Gly Pro Leu Cys Glu Leu Leu Phe 610 615 620 Phe Phe Leu Thr Ala Ile Phe Gln Ala Ile Ala Glu Glu Glu Glu Glu 625 630 635 640 Val Ala Lys Glu Gln Leu Thr Asp Ala Asp Thr Lys Gly Cys Ser Leu 645 650 655 Lys Ser Leu Asp Leu Asp Ser Cys Thr Leu Ser Glu Ile Leu Arg Leu 660 665 670 His Ile Leu Ala Ser Gly Ala Asp Val Thr Ser Ala Asn Ala Lys Tyr 675 680 685 Arg Tyr Gln Lys Arg Gly Gly Phe Asp Ala Thr Asp Asp Ala Cys Met 690 695 700 Glu Leu Arg Leu Ser Asn Pro Ser Leu Val Lys Lys Leu Ser Ser Thr 705 710 715 720 Ser Val Tyr Asp Leu Thr Pro Gly Glu Lys Met Lys Ile Leu His Ala 725 730 735 Leu Cys Gly Lys Leu Leu Thr Leu Val Ser Thr Arg Asp Phe Ile Glu 740 745 750 Asp Tyr Val Asp Ile Leu Arg Gln Ala Lys Gln Glu Phe Arg Glu Leu 755 760 765 Lys Ala Glu Gln His Arg Lys Glu Arg Glu Glu Ala Ala Ala Arg Ile 770 775 780 Arg Lys Arg Lys Glu Glu Lys Leu Lys Glu Gln Glu Gln Lys Met Lys 785 790 795 800 Glu Lys Gln Glu Lys Leu Lys Glu Asp Glu Gln Arg Asn Ser Thr Ala 805 810 815 Asp Ile Ser Ile Gly Glu Glu Glu Arg Glu Asp Phe Asp Thr Ser Ile 820 825 830 Glu Ser Lys Asp Thr Glu Gln Lys Glu Leu Asp Gln Asp Met Phe Thr 835 840 845 Glu Asp Glu Asp Asp Pro Gly Ser His Lys Arg Gly Arg Arg Gly Lys 850 855 860 Arg Gly Gln Asn Gly Phe Lys Glu Phe Thr Arg Gln Glu Gln Ile Asn 865 870 875 880 Cys Val Thr Arg Glu Leu Leu Thr Ala Asp Glu Glu Glu Ala Leu Lys 885 890 895 Gln Glu His Gln Arg Lys Glu Lys Glu Leu Leu Glu Lys Leu Gln Ser 900 905 910 Ala Ile Ala Cys Thr Asn Ile Phe Pro Leu Gly Arg Asp Arg Met Tyr 915 920 925 Arg Arg Tyr Trp Ile Phe Pro Ser Leu Pro Gly Leu Phe Ile Glu Glu 930 935 940 Asp Tyr Ser Gly Leu Thr Glu Asp His Leu Leu Pro Arg Pro Ser Ser 945 950 955 960 Phe Gln Asn Asn Val Gln Ser Gln Asp Pro Gln Val Ser Thr Lys Thr 965 970 975 Gly Glu Pro Leu Met Ser Glu Ser Thr Ser Asn Ile Asp Gln Gly Pro 980 985 990 Arg Asp His Ser Val Gln Leu Pro Lys Pro Val His Lys Pro Asn Arg 995 1000 1005 Trp Cys Phe Tyr Ser Ser Cys Glu Gln Leu Asp Gln Leu Ile Glu Ala 1010 1015 1020 Leu Asn Ser Arg Gly His Arg Glu Ser Ala Leu Lys Glu Thr Leu Leu 1025 1030 1035 1040 Gln Glu Lys Ser Arg Ile Cys Ala Gln Leu Ala Arg Phe Ser Glu Glu 1045 1050 1055 Lys Phe His Phe Ser Asp Lys Arg Gln Pro Asp Ser Lys Pro Thr Tyr 1060 1065 1070 Ser Arg Gly Arg Ser Ser Asn Ala Tyr Asp Pro Ser Gln Met Cys Ala 1075 1080 1085 Glu Lys Gln Leu Glu Leu Arg Leu Arg Asp Phe Leu Leu Asp Ile Glu 1090 1095 1100 Asp Arg Ile Tyr Gln Gly Thr Leu Gly Ala Ile Lys Val Thr Asp Arg 1105 1110 1115 1120 His Ile Trp Arg Ser Ala Leu Glu Ser Gly Arg Tyr Glu Leu Leu Ser 1125 1130 1135 Glu Glu Asn Lys Glu Asn Gly Ile Ile Lys Thr Val Asn Glu Asp Val 1140 1145 1150 Glu Glu Met Glu Ile Asp Glu Gln Thr Lys Val Ile Val Lys Asp Arg 1155 1160 1165 Leu Leu Gly Ile Lys Thr Glu Thr Pro Ser Thr Val Ser Thr Asn Ala 1170 1175 1180 Ser Thr Pro Gln Ser Val Ser Ser Val Val His Tyr Leu Ala Met Ala 1185 1190 1195 1200 Leu Phe Gln Ile Glu Gln Gly Leu Glu Arg Arg Phe Leu Lys Ala Pro 1205 1210 1215 Leu Asp Ala Ser Asp Ser Gly Arg Ser Tyr Lys Thr Val Leu Asp Arg 1220 1225 1230 Trp Arg Glu Ser Leu Leu Ser Ser Ala Ser Leu Ser Gln Val Phe Leu 1235 1240 1245 His Leu Ser Thr Leu Asp Arg Ser Val Ile Trp Ser Lys Ser Ile Leu 1250 1255 1260 Asn Ala Arg Cys Lys Ile Cys Arg Lys Lys Gly Asp Ala Glu Asn Met 1265 1270 1275 1280 Val Leu Cys Asp Gly Cys Asp Arg Gly His His Thr Tyr Cys Val Arg 1285 1290 1295 Pro Lys Leu Lys Ile Val Pro Glu Gly Asp Trp Phe Cys Pro Glu Cys 1300 1305 1310 Arg Pro Lys Gln Arg Cys Arg Arg Leu Ser Phe Arg Gln Arg Pro Ser 1315 1320 1325 Leu Glu Ser Asp Glu Asp Val Glu Asp Ser Met Gly Gly Glu Asp Asp 1330 1335 1340 Glu Val Asp Gly Asp Glu Glu Glu Gly Gln Ser Glu Glu Glu Glu Tyr 1345 1350 1355 1360 Glu Val Glu Gln Asp Glu Asp Asp Ser Gln Glu Glu Glu Glu Val Ser 1365 1370 1375 Leu Pro Lys Arg Gly Arg Pro Gln Val Arg Leu Pro Val Lys Thr Arg 1380 1385 1390 Gly Lys Leu Ser Ser Ser Phe Ser Ser Arg Gly Gln Gln Gln Glu Pro 1395 1400 1405 Gly Arg Tyr Pro Ser Arg Ser Gln Gln Ser Thr Pro Lys Thr Thr Val 1410 1415 1420 Ser Ser Lys Thr Gly Arg Ser Leu Arg Lys Ile Asn Ser Ala Pro Pro 1425 1430 1435 1440 Thr Glu Thr Lys Ser Leu Arg Ile Ala Ser Arg Ser Thr Arg His Ser 1445 1450 1455 His Gly Pro Leu Gln Ala Asp Val Phe Val Glu Leu Leu Ser Pro Arg 1460 1465 1470 Arg Lys Arg Arg Gly Arg Lys Ser Ala Asn Asn Thr Pro Glu Asn Ser 1475 1480 1485 Pro Asn Phe Pro Asn Phe Arg Val Ile Ala Thr Lys Ser Ser Glu Gln 1490 1495 1500 Ser Arg Ser Val Asn Ile Ala Ser Lys Leu Ser Leu Gln Glu Ser Glu 1505 1510 1515 1520 Ser Lys Arg Arg Cys Arg Lys Arg Gln Ser Pro Glu Pro Ser Pro Val 1525 1530 1535 Thr Leu Gly Arg Arg Ser Ser Gly Arg Gln Gly Gly Val His Glu Leu 1540 1545 1550 Ser Ala Phe Glu Gln Leu Val Val Glu Leu Val Arg His Asp Asp Ser 1555 1560 1565 Trp Pro Phe Leu Lys Leu Val Ser Lys Ile Gln Val Pro Asp Tyr Tyr 1570 1575 1580 Asp Ile Ile Lys Lys Pro Ile Ala Leu Asn Ile Ile Arg Glu Lys Val 1585 1590 1595 1600 Asn Lys Cys Glu Tyr Lys Leu Ala Ser Glu Phe Ile Asp Asp Ile Glu 1605 1610 1615 Leu Met Phe Ser Asn Cys Phe Glu Tyr Asn Pro Arg Asn Thr Ser Glu 1620 1625 1630 Ala Lys Ala Gly Thr Arg Leu Gln Ala Phe Phe His Ile Gln Ala Gln 1635 1640 1645 Lys Leu Gly Leu His Val Thr Pro Ser Asn Val Asp Gln Val Ser Thr 1650 1655 1660 Pro Pro Ala Ala Lys Lys Ser Arg Ile 1665 1670 71 1876 PRT Homo sapiens 71 Met Glu Met Glu Ala Asn Glu Ala Asn Asp His Phe Asn Phe Thr Gly 1 5 10 15 Leu Pro Pro Ala Pro Ala Ala Ser Gly Leu Lys Pro Ser Pro Ser Ser 20 25 30 Gly Glu Gly Leu Tyr Thr Asn Gly Ser Pro His Asn Phe Pro Gln Gln 35 40 45 Gly Lys Ser Leu Asn Gly Asp Val Asn Val Asn Gly Leu Ser Thr Val 50 55 60 Ser His Thr Thr Thr Ser Gly Ile Leu Asn Ser Ala Pro His Ser Ser 65 70 75 80 Ser Thr Ser His Leu His His Pro Ser Val Ala Tyr Asp Cys Leu Trp 85 90 95 Asn Tyr Ser Gln Tyr Pro Ser Ala Asn Pro Gly Ser Asn Leu Lys Asp 100 105 110 Pro Pro Leu Leu Ser Gln Phe Ser Gly Gly Gln Tyr Pro Leu Asn Gly 115 120 125 Ile Leu Gly Gly Ser Arg Gln Pro Ser Ser Pro Ser His Asn Thr Asn 130 135 140 Leu Arg Ala Gly Ser Gln Lys Phe Trp Ala Asn Gly Thr His Ser Pro 145 150 155 160 Met Gly Leu Asn Phe Asp Ser Gln Glu Leu Tyr Asp Ser Phe Pro Asp 165 170 175 Gln Asn Phe Glu Glu Val Cys Ser Gly Ile His Pro Asp Glu Ala Ala 180 185 190 Glu Lys Glu Met Thr Ser Val Val Ala Glu Asn Gly Thr Gly Leu Val 195 200 205 Cys Ser Leu Glu Leu Glu Glu Glu Gln Pro Glu Leu Lys Met Cys Gly 210 215 220 Tyr Asn Gly Ser Val Pro Ser Val Glu Ser Leu His Gln Glu Val Ser 225 230 235 240 Val Leu Val Pro Asp Pro Thr Val Ser Cys Leu Asp Asp Pro Ser His 245 250 255 Leu Pro Asp Gln Leu Glu Asp Thr Pro Ile Leu Ser Glu Asp Ser Leu 260 265 270 Glu Pro Phe Asn Ser Leu Ala Pro Glu Pro Val Ser Gly Gly Leu Tyr 275 280 285 Gly Ile Asp Asp Thr Glu Leu Met Gly Ala Glu Asp Lys Leu Pro Leu 290 295 300 Glu Asp Ser Pro Val Ile Ser Ala Leu Asp Cys Pro Ser Leu Asn Asn 305 310 315 320 Ala Thr Ala Phe Ser Leu Leu Ala Asp Asp Ser Gln Thr Ser Thr Ser 325 330 335 Ile Phe Ala Ser Pro Thr Ser Pro Pro Val Leu Gly Glu Ser Val Leu 340 345 350 Gln Asp Asn Ser Phe Asp Leu Asn Asn Gly Ser Asp Ala Glu Gln Glu 355 360 365 Glu Met Glu Thr Gln Ser Ser Asp Phe Pro Pro Ser Leu Thr Gln Pro 370 375 380 Ala Pro Asp Gln Ser Ser Thr Ile Gln Leu His Pro Ala Thr Ser Pro 385 390 395 400 Ala Val Ser Pro Thr Thr Ser Pro Ala Val Ser Leu Val Val Ser Pro 405 410 415 Ala Ala Ser Pro Glu Ile Ser Pro Glu Val Cys Pro Ala Ala Ser Thr 420 425 430 Val Val Ser Pro Ala Val Phe Ser Val Val Ser Pro Ala Ser Ser Ala 435 440 445 Val Leu Pro Ala Val Ser Leu Glu Val Pro Leu Thr Ala Ser Val Thr 450 455 460 Ser Pro Lys Ala Ser Pro Val Thr Ser Pro Ala Ala Ala Phe Pro Thr 465 470 475 480 Ala Ser Pro Ala Asn Lys Asp Val Ser Ser Phe Leu Glu Thr Thr Ala 485 490 495 Asp Val Glu Glu Ile Thr Gly Glu Gly Leu Thr Ala Ser Gly Ser Gly 500 505 510 Asp Val Met Arg Arg Arg Ile Ala Thr Pro Glu Glu Val Arg Leu Pro 515 520 525 Leu Gln His Gly Trp Arg Arg Glu Val Arg Ile Lys Lys Gly Ser His 530 535 540 Arg Trp Gln Gly Glu Thr Trp Tyr Tyr Gly Pro Cys Gly Lys Arg Met 545 550 555 560 Lys Gln Phe Pro Glu Val Ile Lys Tyr Leu Ser Arg Asn Leu Val His 565 570 575 Ser Val Arg Arg Glu His Phe Ser Phe Ser Pro Arg Met Pro Val Gly 580 585 590 Asp Phe Phe Glu Glu Arg Asp Thr Pro Glu Gly Leu Gln Trp Val Gln 595 600 605 Leu Ser Ala Glu Glu Ile Pro Ser Arg Ile Gln Ala Ile Thr Gly Lys 610 615 620 Arg Gly Arg Pro Arg Asn Thr Glu Lys Ala Lys Thr Lys Glu Val Pro 625 630 635 640 Lys Val Lys Arg Gly Arg Gly Arg Pro Pro Lys Val Lys Ile Thr Glu 645 650 655 Leu Leu Asn Lys Thr Asp Asn Arg Pro Leu Lys Lys Leu Glu Ala Gln 660 665 670 Glu Thr Leu Asn Glu Glu Asp Lys Ala Lys Ile Ala Lys Ser Lys Lys 675 680 685 Lys Met Arg Gln Lys Val Gln Arg Gly Glu Cys Leu Thr Thr Ile Gln 690 695 700 Gly Gln Ala Arg Asn Lys Phe Lys Gln Glu Thr Lys Ser Leu Lys His 705 710 715 720 Lys Glu Ala Lys Lys Lys Ser Lys Ala Glu Lys Glu Arg Gly Lys Thr 725 730 735 Lys Gln Glu Lys Leu Lys Glu Lys Val Lys Arg Glu Lys Lys Glu Lys 740 745 750 Val Lys Lys Glu Lys Glu Glu Val Thr Lys Ala Lys Pro Ala Cys Lys 755 760 765 Ala Asp Lys Thr Leu Ala Thr Gln Arg Arg Leu Glu Glu Arg Gln Lys 770 775 780 Gln Gln Met Ile Leu Glu Glu Met Lys Lys Pro Thr Glu Asp Met Cys 785 790 795 800 Leu Thr Asp His Gln Pro Leu Pro Asp Phe Ser Arg Val Pro Gly Leu 805 810 815 Thr Leu Pro Ser Gly Ala Phe Ser Asp Cys Leu Thr Ile Val Glu Phe 820 825 830 Leu His Ser Pro Gly Lys Val Leu Gly Phe Asp Pro Ala Lys Asp Val 835 840 845 Pro Ser Leu Gly Val Leu Gln Glu Gly Leu Leu Cys Gln Gly Asp Ser 850 855 860 Leu Gly Glu Val Gln Asp Leu Leu Val Arg Leu Leu Lys Ala Ala Leu 865 870 875 880 His Asp Pro Gly Phe Pro Ser Tyr Cys Gln Ser Lys Lys Ile Leu Gly 885 890 895 Glu Lys Val Ser Glu Ile Pro Leu Thr Arg Asp Asn Val Ser Glu Ile 900 905 910 Leu Arg Cys Phe Leu Met Ala Tyr Gly Val Glu Pro Ala Leu Cys Asp 915 920 925 Arg Leu Arg Thr Gln Pro Phe Gln Ala Gln Pro Pro Gln Gln Lys Ala 930 935 940 Ala Val Leu Ala Phe Pro Val His Glu Leu Asn Gly Ser Thr Leu Ile 945 950 955 960 Ile Asn Glu Ile Asp Lys Thr Leu Glu Ser Met Ser Ser Tyr Arg Lys 965 970 975 Asn Lys Trp Ile Val Glu Gly Arg Leu Arg Arg Leu Lys Thr Val Leu 980 985 990 Ala Lys Arg Thr Gly Arg Ser Glu Val Glu Met Gly Arg Pro Glu Glu 995 1000 1005 Cys Leu Gly Arg Arg Arg Ser Ser Arg Ile Met Glu Glu Thr Ser Gly 1010 1015 1020 Met Glu Glu Glu Glu Glu Glu Glu Ser Ile Ala Ala Val Pro Gly Arg 1025 1030 1035 1040 Arg Gly Arg Arg Asp Gly Glu Val Asp Ala Thr Ala Ser Ser Ile Pro 1045 1050 1055 Glu Leu Glu Arg Gln Ile Glu Lys Leu Ser Lys Arg Gln Leu Phe Phe 1060 1065 1070 Arg Lys Lys Leu Leu His Ser Ser Gln Met Leu Arg Ala Val Ser Leu 1075 1080 1085 Gly Gln Asp Arg Tyr Arg Arg Arg Tyr Trp Val Leu Pro Tyr Leu Ala 1090 1095 1100 Gly Ile Phe Val Glu Gly Thr Glu Gly Asn Leu Val Pro Glu Glu Val 1105 1110 1115 1120 Ile Lys Lys Glu Thr Asp Ser Leu Lys Val Ala Ala His Ala Ser Leu 1125 1130 1135 Asn Pro Ala Leu Phe Ser Met Lys Met Glu Leu Ala Gly Ser Asn Thr 1140 1145 1150 Thr Ala Ser Ser Pro Ala Arg Ala Arg Ser Arg Pro Leu Lys Thr Lys 1155 1160 1165 Pro Gly Phe Met Gln Pro Arg Glu Phe Lys Ser Pro Val Arg Gly Gln 1170 1175 1180 Asp Ser Glu Gln Pro Gln Ala Gln Leu Gln Pro Glu Ala Gln Leu His 1185 1190 1195 1200 Val Pro Ala Gln Pro Gln Pro Gln Leu Gln Leu Gln Leu Gln Ser His 1205 1210 1215 Lys Gly Phe Leu Glu Gln Glu Gly Ser Pro Leu Ser Leu Gly Gln Ser 1220 1225 1230 Gln His Asp Leu Ser Gln Ser Ala Phe Leu Ser Trp Leu Ser Gln Thr 1235 1240 1245 Gln His Ser Ser Leu Leu Ser Ser Ser Val Leu Thr Pro Asp Ser Ser 1250 1255 1260 Pro Gly Lys Leu Asp Pro Ala Pro Ser Gln Pro Pro Glu Glu Pro Glu 1265 1270 1275 1280 Pro Asp Glu Ala Glu Ser Ser Pro Asp Leu Gln Ala Phe Trp Phe Asn 1285 1290 1295 Ile Ser Ala Gln Met Pro Cys Asn Ala Ala Pro Thr Pro Pro Leu Ala 1300 1305 1310 Val Ser Glu Asp Gln Pro Thr Pro Ser Pro Gln Gln Leu Ala Ser Ser 1315 1320 1325 Lys Pro Met Asn Arg Pro Ser Ala Ala Asn Pro Cys Ser Pro Val Gln 1330 1335 1340 Phe Ser Ser Thr Pro Leu Ala Gly Leu Ala Pro Lys Arg Arg Ala Gly 1345 1350 1355 1360 Asp Pro Gly Glu Met Pro Gln Ser Pro Thr Gly Leu Gly Gln Pro Lys 1365 1370 1375 Arg Arg Gly Arg Pro Pro Ser Lys Phe Phe Lys Gln Met Glu Gln Arg 1380 1385 1390 Val Leu Thr Gln Leu Thr Ala Gln Pro Val Pro Pro Glu Met Cys Ser 1395 1400 1405 Gly Trp Trp Trp Ile Pro Asp Pro Glu Met Leu Asp Ala Met Leu Lys 1410 1415 1420 Ala Leu His Pro Arg Gly Ile Arg Glu Lys Ala Leu His Lys His Leu 1425 1430 1435 1440 Asn Lys His Arg Asp Phe Leu Gln Glu Val Cys Leu Arg Pro Ser Ala 1445 1450 1455 Asp Pro Ile Pro Glu Pro Arg Gln Leu Pro Ala Phe Gln Glu Gly Ile 1460 1465 1470 Met Ser Trp Ser Pro Lys Glu Lys Thr Tyr Glu Thr Asp Leu Ala Val 1475 1480 1485 Leu Gln Trp Val Glu Glu Leu Glu Gln Arg Val Ile Met Ser Asp Leu 1490 1495 1500 Gln Ile Arg Gly Trp Thr Cys Pro Ser Pro Asp Ser Thr Arg Glu Asp 1505 1510 1515 1520 Leu Ala Tyr Cys Glu His Leu Ser Asp Ser Gln Glu Asp Ile Thr Trp 1525 1530 1535 Arg Gly Pro Gly Arg Glu Gly Leu Ala Pro Gln Arg Lys Thr Thr Asn 1540 1545 1550 Pro Leu Asp Leu Ala Val Met Arg Leu Ala Ala Leu Glu Gln Asn Val 1555 1560 1565 Lys Arg Arg Tyr Leu Arg Glu Pro Leu Trp Pro Thr His Glu Trp Val 1570 1575 1580 Leu Glu Lys Ala Leu Leu Ser Thr Pro Asn Gly Ala Pro Glu Gly Thr 1585 1590 1595 1600 Thr Thr Glu Ile Ser Tyr Glu Ile Thr Pro Arg Ile Arg Ile Trp Arg 1605 1610 1615 Gln Thr Leu Gln Arg Cys Arg Ser Ala Ala His Val Cys Leu Cys Leu 1620 1625 1630 Gly His Leu Glu Arg Ser Ile Ala Trp Glu Lys Ser Val Asn Lys Val 1635 1640 1645 Thr Cys Leu Val Cys Arg Lys Gly Asp Asn Asp Glu Phe Leu Leu Leu 1650 1655 1660 Cys Asp Gly Cys Asp Arg Gly Cys His Ile Tyr Cys His Arg Pro Lys 1665 1670 1675 1680 Met Glu Ala Val Pro Glu Gly Asp Trp Phe Cys Thr Val Cys Leu Ala 1685 1690 1695 Gln Gln Val Glu Gly Glu Phe Thr Gln Lys Pro Gly Phe Pro Lys Arg 1700 1705 1710 Gly Gln Lys Arg Lys Ser Gly Tyr Ser Leu Asn Phe Ser Glu Gly Asp 1715 1720 1725 Gly Arg Arg Arg Arg Val Leu Leu Lys Gly Arg Glu Ser Pro Ala Ala 1730 1735 1740 Gly Pro Arg Tyr Ser Glu Glu Arg Leu Ser Pro Ser Lys Arg Arg Pro 1745 1750 1755 1760 Leu Ser Met Arg Asn His His Ser Asp Leu Thr Phe Cys Glu Ile Ile 1765 1770 1775 Leu Met Glu Met Glu Ser His Asp Ala Ala Trp Pro Phe Leu Glu Pro 1780 1785 1790 Val Asn Pro Arg Leu Val Ser Gly Tyr Arg Arg Ile Ile Lys Asn Pro 1795 1800 1805 Met Asp Phe Ser Thr Met Arg Glu Arg Leu Leu Arg Gly Gly Tyr Thr 1810 1815 1820 Ser Ser Glu Glu Phe Ala Ala Asp Ala Leu Leu Val Phe Asp Asn Cys 1825 1830 1835 1840 Gln Thr Phe Asn Glu Asp Asp Ser Glu Val Gly Lys Ala Gly His Ile 1845 1850 1855 Met Arg Arg Phe Phe Glu Ser Arg Trp Glu Glu Phe Tyr Gln Gly Lys 1860 1865 1870 Gln Ala Asn Leu 1875 72 1969 PRT Homo sapiens 72 Met Gly Gln Thr Lys Ser Thr Ser Ser Gly Gly Gly Asn Arg Lys Cys 1 5 10 15 Asn Gln Glu Gln Ser Lys Asn Gln Pro Leu Asp Ala Arg Val Asp Lys 20 25 30 Ile Lys Asp Lys Lys Pro Arg Lys Lys Ala Met Glu Ser Ser Ser Asn 35 40 45 Ser Asp Ser Asp Ser Gly Thr Ser Ser Asp Thr Ser Ser Glu Gly Ile 50 55 60 Ser Ser Ser Asp Ser Asp Asp Leu Glu Glu Asp Glu Glu Glu Glu Asp 65 70 75 80 Gln Ser Ile Glu Glu Ser Glu Asp Asp Asp Ser Asp Ser Glu Ser Glu 85 90 95 Ala Gln His Lys Ser Asn Asn Gln Val Leu Leu His Gly Ile Ser Asp 100 105 110 Pro Lys Ala Asp Gly Gln Lys Ala Thr Glu Lys Ala Gln Glu Lys Arg 115 120 125 Ile His Gln Pro Leu Pro Leu Ala Phe Glu Ser Gln Thr His Ser Phe 130 135 140 Gln Ser Gln Gln Lys Gln Pro Gln Val Leu Ser Gln Gln Leu Pro Phe 145 150 155 160 Ile Phe Gln Ser Ser Gln Ala Lys Glu Glu Ser Val Asn Lys His Thr 165 170 175 Ser Val Ile Gln Ser Thr Gly Leu Val Ser Asn Val Lys Pro Leu Ser 180 185 190 Leu Val Asn Gln Ala Lys Lys Glu Thr Tyr Met Lys Leu Ile Val Pro 195 200 205 Ser Pro Asp Val Leu Lys Ala Gly Asn Lys Asn Thr Ser Glu Glu Ser 210 215 220 Ser Leu Leu Thr Ser Glu Leu Arg Ser Lys Arg Glu Gln Tyr Lys Gln 225 230 235 240 Ala Phe Pro Ser Gln Leu Lys Lys Gln Glu Ser Ser Lys Ser Leu Lys 245 250 255 Lys Val Ile Ala Ala Leu Ser Asn Pro Lys Ala Thr Ser Ser Ser Pro 260 265 270 Ala His Pro Lys Gln Thr Leu Glu Asn Asn His Pro Asn Pro Phe Leu 275 280 285 Thr Asn Ala Leu Leu Gly Asn His Gln Pro Asn Gly Val Ile Gln Ser 290 295 300 Val Ile Gln Glu Ala Pro Leu Ala Leu Thr Thr Lys Thr Lys Met Gln 305 310 315 320 Ser Lys Ile Asn Glu Asn Ile Ala Ala Ala Ser Ser Thr Pro Phe Ser 325 330 335 Ser Pro Val Asn Leu Ser Thr Ser Gly Arg Arg Thr Pro Gly Asn Gln 340 345 350 Thr Pro Val Met Pro Ser Ala Ser Pro Ile Leu His Ser Gln Gly Lys 355 360 365 Glu Lys Ala Val Ser Asn Asn Val Asn Pro Val Lys Thr Gln His His 370 375 380 Ser His Pro Ala Lys Ser Leu Val Glu Gln Phe Arg Gly Thr Asp Ser 385 390 395 400 Asp Ile Pro Ser Ser Lys Asp Ser Glu Asp Ser Asn Glu Asp Glu Glu 405 410 415 Glu Asp Asp Glu Glu Glu Asp Glu Glu Asp Glu Asp Asp Glu Ser Asp 420 425 430 Asp Ser Gln Ser Glu Ser Asp Ser Asn Ser Glu Ser Asp Thr Glu Gly 435 440 445 Ser Glu Glu Glu Asp Asp Asp Asp Lys Asp Gln Asp Glu Ser Asp Ser 450 455 460 Asp Thr Glu Gly Glu Lys Thr Ser Met Lys Leu Asn Lys Thr Thr Ser 465 470 475 480 Ser Lys Ser Pro Ser Met Ser Leu Thr Gly His Ser Thr Pro Arg Asn 485 490 495 Leu His Ile Ala Lys Ala Pro Gly Ser Ala Pro Ala Ala Leu Cys Ser 500 505 510 Glu Ser Gln Ser Pro Ala Phe Leu Gly Thr Ser Ser Ser Thr Leu Thr 515 520 525 Ser Ser Pro His Ser Gly Thr Ser Lys Arg Arg Arg Val Thr Asp Glu 530 535 540 Arg Glu Leu Arg Leu Pro Leu Glu Tyr Gly Trp Gln Arg Glu Thr Arg 545 550 555 560 Ile Arg Asn Phe Gly Gly Arg Leu Gln Gly Glu Val Ala Tyr Tyr Ala 565 570 575 Pro Cys Gly Lys Lys Leu Arg Gln Tyr Pro Glu Val Ile Lys Tyr Leu 580 585 590 Ser Arg Asn Gly Ile Met Asp Ile Ser Arg Asp Asn Phe Ser Phe Ser 595 600 605 Ala Lys Ile Arg Val Gly Asp Phe Tyr Glu Ala Arg Asp Gly Pro Gln 610 615 620 Glu Met Gln Trp Cys Leu Leu Lys Glu Glu Asp Val Ile Pro Arg Ile 625 630 635 640 Arg Ala Met Glu Gly Arg Arg Gly Arg Pro Pro Asn Pro Asp Arg Gln 645 650 655 Arg Ala Arg Glu Glu Ser Arg Met Arg Arg Arg Lys Gly Arg Pro Pro 660 665 670 Asn Val Gly Asn Ala Glu Phe Leu Asp Asn Ala Asp Ala Lys Leu Leu 675 680 685 Arg Lys Leu Gln Ala Gln Glu Ala Arg Gln Ala Ala Gln Ile Lys Leu 690 695 700 Leu Arg Lys Leu Gln Lys Gln Glu Gln Ala Arg Val Ala Lys Glu Ala 705 710 715 720 Lys Lys Gln Gln Ala Ile Met Ala Ala Glu Glu Lys Arg Lys Gln Lys 725 730 735 Glu Gln Ile Lys Ile His Lys Gln Gln Glu Lys Ile Lys Arg Ile Gln 740 745 750 Gln Ile Arg Met Glu Lys Glu Leu Arg Ala Gln Gln Ile Leu Glu Ala 755 760 765 Lys Lys Lys Lys Lys Glu Glu Ala Ala Asn Ala Lys Leu Leu Glu Ala 770 775 780 Glu Lys Arg Ile Lys Glu Arg Glu Met Arg Arg Gln Gln Ala Val Leu 785 790 795 800 Leu Lys Arg Gln Glu Arg Glu Arg Arg Arg Gln His Met Met Leu Met 805 810 815 Lys Ala Met Glu Ala Arg Lys Lys Ala Glu Glu Lys Glu Arg Leu Lys 820 825 830 Gln Glu Lys Arg Asp Glu Lys Arg Leu Asn Lys Glu Arg Lys Leu Glu 835 840 845 Gln Arg Arg Leu Glu Leu Glu Met Ala Lys Glu Leu Lys Lys Pro Asn 850 855 860 Glu Asp Met Cys Leu Ala Asp Gln Lys Pro Leu Pro Glu Leu Pro Arg 865 870 875 880 Ile Pro Gly Leu Val Leu Ser Gly Ser Thr Phe Ser Asp Cys Leu Met 885 890 895 Val Val Gln Phe Leu Arg Asn Phe Gly Lys Val Leu Gly Phe Asp Val 900 905 910 Asn Ile Asp Val Pro Asn Leu Ser Val Leu Gln Glu Gly Ile Leu Leu 915 920 925 Asn Ile Gly Asp Ser Met Gly Glu Val Gln Asp Leu Leu Val Arg Leu 930 935 940 Leu Ser Ala Ala Val Cys Asp Pro Gly Leu Ile Thr Gly Tyr Lys Ala 945 950 955 960 Lys Thr Ala Leu Gly Glu His Leu Leu Asn Val Gly Val Asn Arg Asp 965 970 975 Asn Val Ser Glu Ile Leu Gln Ile Phe Met Glu Ala His Cys Gly Gln 980 985 990 Thr Glu Leu Thr Glu Ser Leu Lys Thr Lys Ala Phe Gln Ala His Thr 995 1000 1005 Pro Ala Gln Lys Ala Val Leu Ala Phe Leu Ile Asn Glu Leu Ala Cys 1010 1015 1020 Ser Lys Ser Val Val Ser Glu Ile Asp Lys Asn Ile Asp Tyr Met Ser 1025 1030 1035 1040 Asn Leu Arg Arg Asp Lys Asn Val Val Glu Gly Lys Leu Arg Lys Leu 1045 1050 1055 Arg Ile Ile His Ala Lys Lys Thr Gly Lys Arg Asp Thr Ser Gly Gly 1060 1065 1070 Ile Asp Leu Gly Glu Glu Gln His Pro Leu Gly Thr Pro Thr Pro Gly 1075 1080 1085 Arg Lys Arg Arg Arg Lys Gly Gly Asp Ser Asp Tyr Asp Asp Asp Asp 1090 1095 1100 Asp Asp Asp Ser Asp Asp Gln Gly Asp Glu Asp Asp Glu Asp Glu Glu 1105 1110 1115 1120 Asp Lys Glu Asp Gln Lys Gly Lys Lys Thr Asp Ile Cys Glu Asp Glu 1125 1130 1135 Asp Glu Gly Asp Gln Ala Ala Ser Val Glu Glu Leu Glu Lys Gln Ile 1140 1145 1150 Glu Lys Leu Ser Lys Gln Gln Ser Gln Tyr Arg Arg Lys Leu Phe Asp 1155 1160 1165 Ala Ser His Ser Leu Arg Ser Val Met Phe Gly Pro Asp Arg Tyr Arg 1170 1175 1180 Arg Arg Tyr Trp Ile Leu Pro Arg Cys Gly Gly Ile Phe Val Glu Gly 1185 1190 1195 1200 Met Glu Ser Gly Glu Gly Leu Glu Glu Ile Ala Lys Glu Arg Glu Lys 1205 1210 1215 Leu Lys Lys Ala Glu Ser Val Gln Ile Lys Glu Glu Met Phe Glu Thr 1220 1225 1230 Ser Gly Asp Ser Leu Asn Cys Ser Asn Thr Asp His Cys Glu Gln Lys 1235 1240 1245 Glu Asp Leu Lys Glu Lys Asp Asn Thr Asn Leu Phe Leu Gln Lys Pro 1250 1255 1260 Gly Ser Phe Ser Lys Leu Ser Lys Leu Leu Glu Val Ala Lys Met Pro 1265 1270 1275 1280 Pro Glu Ser Glu Val Met Thr Pro Lys Pro Asn Ala Gly Ala Asn Gly 1285 1290 1295 Cys Thr Leu Ser Tyr Gln Asn Ser Gly Lys His Ser Leu Gly Ser Val 1300 1305 1310 Gln Ser Thr Ala Thr Gln Ser Asn Val Glu Lys Ala Asp Ser Asn Asn 1315 1320 1325 Leu Phe Asn Thr Gly Ser Ser Gly Pro Gly Lys Phe Tyr Ser Pro Leu 1330 1335 1340 Pro Asn Asp Gln Leu Leu Lys Thr Leu Thr Glu Lys Asn Arg Gln Trp 1345 1350 1355 1360 Phe Ser Leu Leu Pro Arg Thr Pro Cys Asp Asp Thr Ser Leu Thr His 1365 1370 1375 Ala Asp Met Ser Thr Ala Ser Leu Val Thr Pro Gln Ser Gln Pro Pro 1380 1385 1390 Ser Lys Ser Pro Ser Pro Thr Pro Ala Pro Leu Gly Ser Ser Ala Gln 1395 1400 1405 Asn Pro Val Gly Leu Asn Pro Phe Ala Leu Ser Pro Leu Gln Val Lys 1410 1415 1420 Gly Gly Val Ser Met Met Gly Leu Gln Phe Cys Gly Trp Pro Thr Gly 1425 1430 1435 1440 Val Val Thr Ser Asn Ile Pro Phe Thr Leu Ser Val Pro Ser Leu Gly 1445 1450 1455 Ser Gly Leu Gly Leu Ser Glu Gly Asn Gly Asn Ser Phe Leu Thr Ser 1460 1465 1470 Asn Val Ala Ser Ser Lys Ser Glu Ser Pro Val Pro Gln Asn Glu Lys 1475 1480 1485 Ala Thr Ser Ala Gln Pro Ala Ala Val Glu Val Ala Lys Pro Val Asp 1490 1495 1500 Phe Pro Ser Pro Lys Pro Ile Pro Glu Glu Met Gln Phe Gly Trp Trp 1505 1510 1515 1520 Arg Ile Ile Asp Pro Glu Asp Leu Lys Ala Leu Leu Lys Val Leu His 1525 1530 1535 Leu Arg Gly Ile Arg Glu Lys Ala Leu Gln Lys Gln Ile Gln Lys His 1540 1545 1550 Leu Asp Tyr Ile Thr Gln Ala Cys Leu Lys Asn Lys Asp Val Ala Ile 1555 1560 1565 Ile Glu Leu Asn Glu Asn Glu Glu Asn Gln Val Thr Arg Asp Ile Val 1570 1575 1580 Glu Asn Trp Ser Val Glu Glu Gln Ala Met Glu Met Asp Leu Ser Val 1585 1590 1595 1600 Leu Gln Gln Val Glu Asp Leu Glu Arg Arg Val Ala Ser Ala Ser Leu 1605 1610 1615 Gln Val Lys Gly Trp Met Cys Pro Glu Pro Ala Ser Glu Arg Glu Asp 1620 1625 1630 Leu Val Tyr Phe Glu His Lys Ser Phe Thr Lys Leu Cys Lys Glu His 1635 1640 1645 Asp Gly Glu Phe Thr Gly Glu Asp Glu Ser Ser Ala His Ala Leu Glu 1650 1655 1660 Arg Lys Ser Asp Asn Pro Leu Asp Ile Ala Val Thr Arg Leu Ala Asp 1665 1670 1675 1680 Leu Glu Arg Asn Ile Glu Arg Arg Ile Glu Glu Asp Ile Ala Pro Gly 1685 1690 1695 Leu Arg Val Trp Arg Arg Ala Leu Ser Glu Ala Arg Ser Ala Ala Gln 1700 1705 1710 Val Ala Leu Cys Ile Gln Gln Leu Gln Lys Ser Ile Ala Trp Glu Lys 1715 1720 1725 Ser Ile Met Lys Val Tyr Cys Gln Ile Cys Arg Lys Gly Asp Asn Glu 1730 1735 1740 Glu Leu Leu Leu Leu Cys Asp Gly Cys Asp Lys Gly Cys His Thr Tyr 1745 1750 1755 1760 Cys His Arg Pro Lys Ile Thr Thr Ile Pro Asp Gly Asp Trp Phe Cys 1765 1770 1775 Pro Ala Cys Ile Ala Lys Ala Ser Gly Gln Thr Leu Lys Ile Lys Lys 1780 1785 1790 Leu His Val Lys Gly Lys Lys Thr Asn Glu Ser Lys Lys Gly Lys Lys 1795 1800 1805 Val Thr Leu Thr Gly Asp Thr Glu Asp Glu Asp Ser Ala Ser Thr Ser 1810 1815 1820 Ser Ser Leu Lys Arg Gly Asn Lys Asp Leu Gln Lys Arg Lys Met Glu 1825 1830 1835 1840 Glu Asn Thr Ser Ile Asn Leu Ser Lys Gln Glu Ser Phe Thr Ser Val 1845 1850 1855 Lys Lys Pro Lys Arg Asp Asp Ser Lys Asp Leu Ala Leu Cys Ser Met 1860 1865 1870 Ile Leu Thr Glu Met Glu Thr His Glu Asp Ala Trp Pro Phe Leu Leu 1875 1880 1885 Pro Val Asn Leu Lys Leu Val Pro Gly Tyr Lys Lys Val Ile Lys Lys 1890 1895 1900 Pro Met Asp Phe Ser Thr Ile Arg Glu Lys Leu Ser Ser Gly Gln Tyr 1905 1910 1915 1920 Pro Asn Leu Glu Thr Phe Ala Leu Asp Val Arg Leu Val Phe Asp Asn 1925 1930 1935 Cys Glu Thr Phe Trp Glu Asp Asp Ser Asp Ile Gly Arg Ala Gly His 1940 1945 1950 Asn Met Arg Lys Tyr Phe Glu Lys Lys Trp Thr Asp Thr Phe Lys Val 1955 1960 1965 Ser 73 12 DNA Homo sapiens 73 tacagaccct cc 12 

What is claimed is:
 1. A substantially pure polypeptide comprising an amino acid sequence at least 60% identical to any one of SEQ ID NOs: 1, 13, 21, 27, or 29, wherein the polypeptide regulates transcription of a gene and comprises a bromodomain.
 2. The polypeptide of claim 1, wherein the amino acid sequence is at least 70% identical to any one of SEQ ID NOs: 1, 13, 21, 27, or
 29. 3. The polypeptide of claim 1, wherein the amino acid sequence is at least 80% identical to any one of SEQ ID NOs: 1, 13, 21, 27, or
 29. 4. The polypeptide of claim 1, wherein the amino acid sequence is at least 90% identical to any one of SEQ ID NOs: 1, 13, 21, 27 or
 29. 5. A substantially pure polypeptide comprising any one of SEQ ID NOs: 1, 13, 21, 27, or
 29. 6. A substantially pure polypeptide comprising the amino acid sequence of any one of SEQ ID NOs: 1, 13, 21, 27, or 29, with up to 30 conservative amino acid substitutions, wherein the polypeptide regulates transcription of a gene and comprises a bromodomain.
 7. A substantially pure polypeptide encoded by a nucleic acid that hybridizes under high stringency conditions to a probe the sequence of which consists of any one of SEQ ID NOs: 2, 14, 22, 28, or 30, wherein the polypeptide regulates transcription of a gene and comprises a bromodomain.
 8. An isolated nucleic acid encoding the polypeptide of claim
 1. 9. An isolated nucleic acid encoding the polypeptide of claim
 5. 10. An isolated nucleic acid encoding the polypeptide of claim
 6. 11. An isolated nucleic acid comprising a strand that hybridizes under high stringency conditions to a single stranded probe consisting of any one of SEQ ID NOs: 2, 14, 22, 28, or
 30. 12. The isolated nucleic acid of claim 11, wherein the nucleic acid encodes a polypeptide that regulates transcription of a gene and comprises a bromodomain.
 13. The nucleic acid of claim 12, wherein the polypeptide comprises any one of SEQ ID NOs: 1, 13, 21, 27, or
 29. 14. The nucleic acid of claim 11, wherein the strand is at least 15 nucleotides in length.
 15. A vector comprising the nucleic acid of claim
 8. 16. A vector comprising the nucleic acid of claim
 9. 17. A vector comprising the nucleic acid of claim
 10. 18. A vector comprising the nucleic acid of claim
 11. 19. A vector comprising the nucleic acid of claim
 12. 20. A cultured host cell comprising the nucleic acid of claim
 8. 21. A cultured host cell comprising the nucleic acid of claim
 9. 22. A cultured host cell comprising the nucleic acid of claim
 10. 23. A cultured host cell comprising the nucleic acid of claim
 11. 24. A cultured host cell comprising the nucleic acid of claim
 12. 25. An antibody that specifically binds to the polypeptide of claim
 1. 26. A method of preparing a polypeptide, the method comprising culturing the host cell of claim 20, wherein the host cell expresses the polypeptide, and isolating the polypeptide from the host cell.
 27. A method of screening for a compound that binds to a polypeptide, the method comprising providing a polypeptide comprising an amino acid sequence at least 60% identical to SEQ ID NO: 1; contacting a test compound with the polypeptide; and determining whether the test compound has bound to the polypeptide.
 28. A compound which specifically binds to the polypeptide of claim
 1. 